The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy
AbstractCheckpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immu...
Source: Cancer Immunology, Immunotherapy - November 9, 2017 Category: Cancer & Oncology Source Type: research

Tumor-derived high-mobility group box 1 and thymic stromal lymphopoietin are involved in modulating dendritic cells to activate T regulatory cells in a mouse model
AbstractHigh-mobility group box 1 (HMGB1) is involved in the tumor-associated activation of regulatory T cells (Treg), but the mechanisms remain unknown. In a mouse tumor model, silencing HMGB1 in tumor cells or inhibiting tumor-derived HMGB1 not only dampened the capacity of tumor cells to produce thymic stromal lymphopoietin (TSLP), but also aborted the tumor-associated modulation of Treg-activating DC. Tumor-derived HMGB1 triggered the production of TSLP by tumor cells. Importantly, both tumor-derived HMGB1 and TSLP were necessary for modulating DC to activate Treg in a TSLP receptor (TSLPR)-dependent manner. In the the...
Source: Cancer Immunology, Immunotherapy - November 7, 2017 Category: Cancer & Oncology Source Type: research

BRAF peptide vaccine facilitates therapy of murine BRAF-mutant melanoma
AbstractApproximately, 50% of human melanomas are driven by BRAF mutations, which produce tumors that are highly immunosuppressive and often resistant to vaccine therapy. We introduced lipid-coated calcium phosphate nanoparticles (LCP NPs) as a carrier to efficiently deliver a tumor-specific antigen, the BRAFV600E peptide, to drive dendritic cell (DC) maturation and antigen presentation in C57BL6 mice. The BRAF peptide vaccine elicited a robust, antigen-specific cytotoxic T cell response and potent tumor growth inhibition in a murine BRAF-mutant melanoma model. Advanced BRAF-specific immune response was illustrated by IFN-...
Source: Cancer Immunology, Immunotherapy - November 1, 2017 Category: Cancer & Oncology Source Type: research

A phase I vaccination study with dendritic cells loaded with NY-ESO-1 and α-galactosylceramide: induction of polyfunctional T cells in high-risk melanoma patients
AbstractVaccines that elicit targeted tumor antigen-specific T-cell responses have the potential to be used as adjuvant therapy in patients with high risk of relapse. However, the responses induced by vaccines in cancer patients have generally been disappointing. To improve vaccine function, we investigated the possibility of exploiting the immunostimulatory capacity of type 1 Natural killer T (NKT) cells, a cell type enriched in lymphoid tissues that can trigger improved antigen-presenting function in dendritic cells (DCs). In this phase I dose escalation study, we treated eight patients with high-risk surgically resected...
Source: Cancer Immunology, Immunotherapy - November 1, 2017 Category: Cancer & Oncology Source Type: research

Cross-talk between TNF- α and IFN-γ signaling in induction of B7-H1 expression in hepatocellular carcinoma cells
AbstractClinical benefit from immunotherapy of B7-H1/PD-1 checkpoint blockade indicates that it is important to understand the regulatory mechanism of B7-H1 expression in cancer cells. As an adaptive response to the endogenous antitumor immunity, B7-H1 expression is up-regulated in HCC cells. B7-H1 expression is induced mainly by IFN- γ released from tumor-infiltrating T cells in HCC. In addition, HCC is a prototype of inflammation-related cancer and TNF-α is a critical component of inflammatory microenvironment of HCC. In the present study, we asked whether TNF-α can promote the expression of B7-H1 induc...
Source: Cancer Immunology, Immunotherapy - October 31, 2017 Category: Cancer & Oncology Source Type: research

CXCL13 expression is prognostic and predictive for postoperative adjuvant chemotherapy benefit in patients with gastric cancer
ConclusionsIntratumoral CXCL13 expression appears as an independent prognostic marker for patients after gastric cancer resection. In addition, CXCL13 expression may serve as a predictive biomarker of response to postoperative adjuvant chemotherapy in these patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 31, 2017 Category: Cancer & Oncology Source Type: research

A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated regression of established solid tumors in mice
AbstractStrong evidence exists supporting the important role T cells play in the immune response against tumors. Still, the ability to initiate tumor-specific immune responses remains a challenge. Recent clinical trials suggest that bispecific antibody-mediated retargeted T cells are a promising therapeutic approach to eliminate hematopoietic tumors. However, this approach has not been validated in solid tumors. PF-06671008 is a dual-affinity retargeting (DART®)-bispecific protein engineered with enhanced pharmacokinetic properties to extend in vivo half-life, and designed to engage and activate endogenous polyclonal T...
Source: Cancer Immunology, Immunotherapy - October 24, 2017 Category: Cancer & Oncology Source Type: research

Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells
We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4+ and CD8+ T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4+ and CD8+ T cells. Parameters monitored on transduced T cells included activation (CD25, CD69), inhibitory (PD-1, TIM-3, CTLA-4), costimulatory (OX40), and memory (CCR7) markers. For the clinical trial, T cells were activated, transduced, selected for CD34t+ cells, then ...
Source: Cancer Immunology, Immunotherapy - October 20, 2017 Category: Cancer & Oncology Source Type: research

Fourteenth Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT) on Cancer Bio-Immunotherapy, Siena, Italy, October 13 –15, 2016
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 20, 2017 Category: Cancer & Oncology Source Type: research

NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma
AbstractThe prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples) protein expression in tumor specimens. T-cells from peripheral blood were stimulated with TAAs (synthetic peptides) in IL-2 and IL-7, or using a combination of IL-2, IL-15 and IL-21. CD4+ and CD8+ T-cells were tested for antigen-specific proliferation by flow cytometry, and IFN- &gamm...
Source: Cancer Immunology, Immunotherapy - October 20, 2017 Category: Cancer & Oncology Source Type: research

Immunotherapy for hepatocellular carcinoma patients: is it ready for prime time?
AbstractHepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second most common cause of cancer death worldwide. Current treatment options for patients with intermediate and advanced HCC are limited, and there is an unmet need for novel therapeutic approaches. HCC is an attractive target for immunomodulation therapy, since it arises in an inflammatory milieu due to hepatitis B and C infections and cirrhosis. However, a major barrier to the development and success of immunotherapy in patients with HCC is the liver ’s inherent immunosuppressive function. Recent advances in the field of can...
Source: Cancer Immunology, Immunotherapy - October 20, 2017 Category: Cancer & Oncology Source Type: research

Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia
AbstractSeveral retrospective studies in children with B cell precursor (BCP) acute lymphoblastic leukemia (ALL) provided clinical evidence that higher absolute lymphocyte counts (ALC) early into treatment significantly correlated with improved relapse-free and overall survival. It still remains unknown, however, whether the predictive role of higher ALCs reflects general bone marrow recovery or a more specific attribute of immune function. To investigate this question, we implemented a prospective observational cohort study in 20 children with BCP ALL on day 29 (D29) of induction chemotherapy and immunophenotyped their ly...
Source: Cancer Immunology, Immunotherapy - October 20, 2017 Category: Cancer & Oncology Source Type: research

Clinicopathologic implications of CD8 + /Foxp3 + ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients
AbstractCurrently, little is known about the interactions between microRNAs (miRNAs) and the PD-1/PD-L1 signaling pathway in chordoma, and data discussing the role of the immune milieu in chordoma prognosis are limited. We aimed to analyze the relationship between PD-L1, miR-574-3p, microenvironmental tumor-infiltrating lymphocytes (TILs) and clinicopathological features of spinal chordoma patients. PD-L1 expression and TILs (including Foxp3+, CD8+, PD-1+ and PD-L1+) were assessed by immunohistochemistry in tumor specimens of 54 spinal chordoma patients. MiRNAs microarray and bioinformatical analysis were used to identify ...
Source: Cancer Immunology, Immunotherapy - October 20, 2017 Category: Cancer & Oncology Source Type: research

Cholecystokinin receptor antagonist alters pancreatic cancer microenvironment and increases efficacy of immune checkpoint antibody therapy in mice
We examined the effects of CCKR antagonists or immune checkpoint blockade antibodies alone or in combination in murine models of PDAC. Monotherapy with CCKR blockade significantly decreased tumor size and metastases in SCID mice with orthotopic PDAC, and in C57BL/6 mice, it reduced fibrosis and induced the influx of TILs. Immune-competent mice bearing syngeneic pancreatic cancer (Panc02 and mT3-2D) that were treated with the combination of CCK receptor antagonists and immune checkpoint blockade antibodies survived significantly longer with smaller tumors. Tumor immunohistochemical staining and flow cytometry demonstrated t...
Source: Cancer Immunology, Immunotherapy - October 17, 2017 Category: Cancer & Oncology Source Type: research

A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer
AbstractColorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated...
Source: Cancer Immunology, Immunotherapy - October 12, 2017 Category: Cancer & Oncology Source Type: research

Quantification of altered tissue turnover in a liquid biopsy: a proposed precision medicine tool to assess chronic inflammation and desmoplasia associated with a pro-cancerous niche and response to immuno-therapeutic anti-tumor modalities
AbstractImmuno-therapy has begun to revolutionize cancer treatment. However, despite the significant progress achieved in regard to the duration of clinical benefits, a substantial number of patients do not respond to these therapies. To improve the outcome of patients receiving immuno-therapy, there is a need for novel biomarkers that can predict and monitor treatment. Tumor microenvironment alterations, more specifically the state of chronic inflammation and desmoplasia (tumor fibrosis), are important factors to consider in this context. Here, we discuss the potential for quantification of altered tissue turnover in a li...
Source: Cancer Immunology, Immunotherapy - October 11, 2017 Category: Cancer & Oncology Source Type: research

Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies
ConclusionArthralgia is frequent during PD1ab treatment. The clinical picture varies between synovitis of predominantly large joints, progressive osteoarthritis and arthralgia without evident joint damage. Vast majority of cases can be satisfactorily managed by NSAID and/or low-dose corticosteroids. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 10, 2017 Category: Cancer & Oncology Source Type: research

Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy
AbstractMonoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most mark...
Source: Cancer Immunology, Immunotherapy - October 7, 2017 Category: Cancer & Oncology Source Type: research

Safety of shortened infusion times for combined ipilimumab and nivolumab
ConclusionsShortened infusion times for combined ipilimumab and nivolumab treatment are safe, thereby facilitating a more efficient use of outpatient facilities and enhancing patient ’s convenience. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 7, 2017 Category: Cancer & Oncology Source Type: research

Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study
AbstractIpilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of  ≥ 10%, or ...
Source: Cancer Immunology, Immunotherapy - October 5, 2017 Category: Cancer & Oncology Source Type: research

Immunological classification of renal cell carcinoma patients based on phenotypic analysis of immune check-point molecules
ConclusionsThis study showed that the presence of classable diversity in the immunological signature of tumour tissue-infiltrating lymphocytes correlated with prognosis and tumour aggressiveness that was observed even within individual tumours in some patients with renal cell carcinoma. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 3, 2017 Category: Cancer & Oncology Source Type: research

Daunorubicin conjugated with alpha-fetoprotein selectively eliminates myeloid-derived suppressor cells (MDSCs) and inhibits experimental tumor growth
AbstractFailure of antitumor immunity in cancer was shown to be mediated by myeloid-derived suppressor cells (MDSCs), which are considered to be one of the key factors contributing to the development of malignant diseases. Therefore, the development of pharmacological approaches to effectively eliminate MDSCs in organisms carrying growing tumors is a promising pathway for potential treatment. For this purpose we propose alpha-fetoprotein (AFP) conjugated with a cytotoxic agent as a vector molecule, specifically recognizing MDSCs. The present study was aimed at examination of this suggestion using both in vitro and in vivo ...
Source: Cancer Immunology, Immunotherapy - September 27, 2017 Category: Cancer & Oncology Source Type: research

Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer
AbstractObjectiveImmunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population.Materials and methodsThe single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continu...
Source: Cancer Immunology, Immunotherapy - September 25, 2017 Category: Cancer & Oncology Source Type: research

Clinical evaluation of macrophages in cancer: role in treatment, modulation and challenges
AbstractThe focus of immunotherapeutics has been placed firmly on anti-tumour T cell responses. Significant progress has been made in the treatment of both local and systemic malignancies, but low response rates and rising toxicities are limiting this approach. Advancements in the understanding of tumour immunology are opening up a new range of therapeutic targets, including immunosuppressive factors in the tumour microenvironment. Macrophages are a heterogeneous group of cells that have roles in innate and adaptive immunity and tissue repair, but become co-opted by tumours to support tumour growth, survival, metastasis an...
Source: Cancer Immunology, Immunotherapy - September 25, 2017 Category: Cancer & Oncology Source Type: research

HLA class I expression predicts prognosis and therapeutic benefits from tyrosine kinase inhibitors in metastatic renal-cell carcinoma patients
In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients.Experimental designA TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon- α-based immunotherapy at a single institution were retrospectively enrolled. HLA class I expression and cytotoxic T lymphocyte (CTL) density was assessed by immunohistochemistry on tissue microarrays. Association between HLA class I and CTL was also assessed in the TCGA KIRC cohort.ResultsIn the TKI cohort, down-re...
Source: Cancer Immunology, Immunotherapy - September 16, 2017 Category: Cancer & Oncology Source Type: research

Monitoring the response of urothelial precancerous lesions to Bacillus Calmette-Guerin at the proteome level in an in vivo rat model
AbstractIntravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. We aimed to monitor changes at the proteome level to identify putative protein biomarkers associated with the response of urothelial precancerous lesions to intravesical BCG treatment. The rats were divided into three groups (n = 10/group): control, non-treated, and BCG-treated groups. The non-treated and BCG-treated groups receivedN-methyl-N-nitrosourea intravesically. BCG Tice-strain was instilled into bladder in BCG-treated group. At the endpoint of experiment, all surviving...
Source: Cancer Immunology, Immunotherapy - September 15, 2017 Category: Cancer & Oncology Source Type: research

Bile duct obstruction in a patient treated with nivolumab as second-line chemotherapy for advanced non-small-cell lung cancer: a case report
AbstractImmune checkpoint inhibitors (ICIs) are becoming a standard therapy for non-small-cell lung cancer in the advanced stage. As these ICIs become widely available in clinical practice, immune-related adverse effects will become more common. Here we report a patient with lung adenocarcinoma who was treated with nivolumab and developed obstruction because of biliary inflammation. A 63-year-old Japanese man having lung adenocarcinoma with pleural dissemination complained of epigastric pain on the fifth cycle of nivolumab. Computed tomography showed wall thickening at the lower part of the bile duct and cholecystitis. End...
Source: Cancer Immunology, Immunotherapy - September 14, 2017 Category: Cancer & Oncology Source Type: research

Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression
AbstractThe delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy...
Source: Cancer Immunology, Immunotherapy - September 13, 2017 Category: Cancer & Oncology Source Type: research

Tumor infiltrating lymphocytes in lymph node metastases of stage III melanoma correspond to response and survival in nine patients treated with ipilimumab at the time of stage IV disease
AbstractPrognosis of metastatic melanoma improved with the development of checkpoint inhibitors. The role of tumor infiltrating lymphocytes (TILs) in lymph node metastases of stage III melanoma remains unclear. We retrospectively characterized TILs in primary melanomas and matched lymph node metastases (stage III melanoma) of patients treated with the checkpoint inhibitor ipilimumab. Tumor infiltrating lymphocytes were characterized for CD3, CD4, and CD8 expressions by immunohistochemistry. 4/9 patients (44%) responded to treatment with ipilimumab (1 complete and 2 partial remissions, 1 stable disease). All responders exhi...
Source: Cancer Immunology, Immunotherapy - September 11, 2017 Category: Cancer & Oncology Source Type: research

Transcriptomic analysis of the tumor microenvironment to guide prognosis and immunotherapies
AbstractTumors are highly heterogeneous tissues where malignant cells are surrounded by and interact with a complex tumor microenvironment (TME), notably composed of a wide variety of immune cells, as well as vessels and fibroblasts. As the dialectical influence between tumor cells and their TME is known to be clinically crucial, we need tools that allow us to study the cellular composition of the microenvironment. In this focused research review, we report MCP-counter, a methodology based on transcriptomic markers that assesses the proportion of several immune and stromal cell populations in the TME from transcriptomic da...
Source: Cancer Immunology, Immunotherapy - September 7, 2017 Category: Cancer & Oncology Source Type: research

Clinical grade manufacturing of genetically modified, CAR-expressing NK-92 cells for the treatment of ErbB2-positive malignancies
ConclusionOur concept suggests NK-92/5.28.z maintenance culture from which therapeutic doses up to 5  × 109 cells can be expanded in 10  L within 5 days. This established process is feasible to analyze NK-92/5.28.z in phase I/II trials. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 6, 2017 Category: Cancer & Oncology Source Type: research

The STAT3 inhibitor pyrimethamine displays anti-cancer and immune stimulatory effects in murine models of breast cancer
We report that PYR shows therapeutic activity in two independent mouse models of breast cancer, with both direct tumor inhibitory and immune stimulatory effects. PYR-inhibited STAT3 activity in TUBO and TM40D-MB metastatic breast cancer cells in vitro and inhibited tumor cell proliferation and invasion into Matrigel basement membrane matrix. In tumor-transplanted mice, PYR had both direct and indirect tumor inhibitory effects. Tumor-bearing mice treated with PYR showed reduced STAT3 activation in tumor cells, attenuated tumor growth, and reduced tumor-associated inflammation. In addition, expression of Lamp1 by tumor infil...
Source: Cancer Immunology, Immunotherapy - September 5, 2017 Category: Cancer & Oncology Source Type: research

Immune profiling of melanoma tumors reflecting aggressiveness in a preclinical model
AbstractMelanoma, like most solid tumors, is highly heterogeneous in terms of invasive, proliferative, and tumor-initiating potential. This heterogeneity is the outcome of differential gene expression resulting from conditions in the tumor microenvironment and the selective pressure of the immune system. To investigate possible signatures combining immune-related gene expression and lymphocyte infiltration, we established a preclinical model using B16.F1-derived clones, in the context of melanoma aggressiveness. Combinatorial analyses revealed that tumors concomitantly expressing low levels ofTnf-a, Pd-1, Il-10, Il-1ra, Cc...
Source: Cancer Immunology, Immunotherapy - September 4, 2017 Category: Cancer & Oncology Source Type: research

Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients
We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade...
Source: Cancer Immunology, Immunotherapy - August 30, 2017 Category: Cancer & Oncology Source Type: research

CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer
AbstractThe ability of some tumors to exclude effector T cells represents a major challenge to immunotherapy. T cell exclusion is particularly evident in pancreatic ductal adenocarcinoma (PDAC), a disease where blockade of the immune checkpoint molecule CTLA-4 has not produced significant clinical activity. In PDAC, effector T cells are often scarce within tumor tissue and confined to peritumoral lymph nodes and lymphoid aggregates. We hypothesized that CTLA-4 blockade, despite a lack of clinical efficacy seen thus far in PDAC, might still alter T cell immunobiology, which would have therapeutic implications. Using clinica...
Source: Cancer Immunology, Immunotherapy - August 30, 2017 Category: Cancer & Oncology Source Type: research

Therapeutic antibodies against cancer stem cells: a promising approach
AbstractMonoclonal antibodies have been extensively used to treat malignancy along with routine chemotherapeutic drugs. Chemotherapy for metastatic cancer has not been successful in securing long-term remission of disease. This is in part due to the resistance of cancer cells to drugs. One aspect of the drug resistance is the inability of conventional drugs to eliminate cancer stem cells (CSCs) which often constitute less than 1 –2% of the whole tumor. In some tumor types, it is possible to identify these cells using surface markers. Monoclonal antibodies targeting these CSCs are an attractive option for a new therap...
Source: Cancer Immunology, Immunotherapy - August 24, 2017 Category: Cancer & Oncology Source Type: research

Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression
In conclusion, our data indicate that IL-6 induces M2 macrophage differentiation (IL-10highTGF- βhighIL-12p35low) by activating STAT3 phosphorylation, and the IL-6-induced M2 macrophages exert a pro-tumor function by promoting GC cell proliferation and migration. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 21, 2017 Category: Cancer & Oncology Source Type: research

Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11)
ConclusionsOur results demonstrate that patients with MBL and PFT exhibit overall reduced CD4+ T cell counts at diagnosis but not an elevated proportion of Tregs. Standard treatment exacerbates lymphopenia in those with MBL while enriching for immunosuppressive Tregs over time. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 20, 2017 Category: Cancer & Oncology Source Type: research

Novel prostate cancer immunotherapy with a DNA-encoded anti-prostate-specific membrane antigen monoclonal antibody
In this report, we describe a novel strategy of antibody-based immunotherapy against prostate carcinoma that utilizes synthetic DNA plasmids that encode a therapeutic human mAb that target PSMA. Electroporation-enhanced intramuscular injection of the DNA-encoded mAb (DMAb) plasmid into mice led to the production of functional and durable levels of the anti-PSMA antibody. The anti-PSMA produced in vivo controlled tumor growth and prolonged survival in a mouse model. This is likely mediated by antibody-dependent cellular cytotoxicity (ADCC) effect with the aid of NK cells. Further study of   this novel approach for trea...
Source: Cancer Immunology, Immunotherapy - August 17, 2017 Category: Cancer & Oncology Source Type: research

Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment
AbstractMucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells ’ potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrati...
Source: Cancer Immunology, Immunotherapy - August 10, 2017 Category: Cancer & Oncology Source Type: research

Atopy and prostate cancer: Is there a link between circulating levels of IgE and PSA in humans?
ConclusionDespite statistical insignificance, the observed trend warrants further research given the increasing evidence of the role of atopy and IgE antibodies in protective responses against tumours. A lifecourse approach of measuring IgE, specific subtypes, and other markers of the humoral immune system (i.e. IgG) could shed more light on its potential anti-cancer characteristics. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 9, 2017 Category: Cancer & Oncology Source Type: research

Evaluation of a xenogeneic vascular endothelial growth factor-2 vaccine in two preclinical metastatic tumor models in mice
In this study, a xenogeneic DNA vaccine encoding for human vascular endothelial growth factor receptor-2 (hVEGFR-2) was evaluated in two murine tumor models, the B16-F10 melanoma and the EO771 breast carcinoma model. The vaccine was administered by intradermal injection followed by electroporation. The immunogenicity and the biological efficacy of the vaccine were tested in (1) a prophylactic setting, (2) a therapeutic setting, and (3) a therapeutic setting combined with surgical removal of the primary tumor. The tumor growth, survival, and development of an immune response were followed. The cellular immune response was m...
Source: Cancer Immunology, Immunotherapy - August 3, 2017 Category: Cancer & Oncology Source Type: research

An unbiased in vivo functional genomics screening approach in mice identifies novel tumor cell-based regulators of immune rejection
AbstractThe clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, thereby parsing the tumor microenvironment complexity into tractable pieces. However, this limits the potential for novel gene discovery to in vivo immune attack. To address this challenge, we developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immune-competent and immunodeficient mice to select for tumor...
Source: Cancer Immunology, Immunotherapy - August 2, 2017 Category: Cancer & Oncology Source Type: research

CAR T cells targeting solid tumors: carcinoembryonic antigen (CEA) proves to be a safe target
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 28, 2017 Category: Cancer & Oncology Source Type: research

IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model
AbstractRecent findings show that immune cells constitute a large fraction of the tumor microenvironment and that they modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL-4, in particular, is upregulated. Thus, we tested whether IL-4 neutralization would affect tumor immunity. Current results demonstrate that the administration of a neutralizing antibody against IL-4 enhances anti-tumor immunity and delays tumor progression. IL-4 blockade also alters inflammation in the tumor microenvironment, reducing the generation of both immunosuppressive M2 macrophages and...
Source: Cancer Immunology, Immunotherapy - July 21, 2017 Category: Cancer & Oncology Source Type: research

Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy
This study aimed at defining the fe atures, function and dynamics of Foxp3+CD25highCD4+ Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival. We observed a pronounced increase in Treg counts in peripheral blood during initial cycles of HDC/IL-2. The accumulating Tregs resembled thymic-derived natural Tregs (nTregs), showed augmented expression of CTLA-4 and suppressed the cell cycle proliferation of conventional T cells ex vivo. Relapse of AML was not prognosticated by Treg counts at onset of treatment or after the first cycle of immunotherapy. However, the magnitude of Tre...
Source: Cancer Immunology, Immunotherapy - July 18, 2017 Category: Cancer & Oncology Source Type: research

Oncolytic immunotherapy: unlocking the potential of viruses to help target cancer
AbstractOncolytic immunotherapy is a research area of cancer immunotherapy investigating the use of modified viruses to target cancer cells. A variety of different viral backbones (e.g., adenovirus, reovirus) with a diverse range of genetic modifications are currently being investigated for the treatment of a variety of cancers. The oncolytic virus that has advanced the furthest in clinical development is talimogene laherparepvec, a recombinant HSV-1 virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF). In a phase 3 study in patients with unresectable metastatic melanoma, intralesional talimogene lahe...
Source: Cancer Immunology, Immunotherapy - July 15, 2017 Category: Cancer & Oncology Source Type: research

Cerebellar degeneration-related proteins 2 and 2-like are present in ovarian cancer in patients with and without Yo antibodies
ConclusionCDR2L is present in ovarian cancers from patients with and without Yo antibodies as was shown previously for CDR2. In addition, both CDR2 and CDR2L proteins are more widely expressed than previously thought, both in normal and cancerous tissues. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 14, 2017 Category: Cancer & Oncology Source Type: research

CTLA-4 expression in the non-small cell lung cancer patient tumor microenvironment: diverging prognostic impact in primary tumors and lymph node metastases
AbstractThe immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 patients with primary resected stage I –IIIA NSCLC. Expression of CTLA-4 was analyzed in tumor and stromal primary tumor tissue and in locoregional metastatic lymph nodes. CTLA-4 expression in neither tumor epithel...
Source: Cancer Immunology, Immunotherapy - July 13, 2017 Category: Cancer & Oncology Source Type: research

“Tumor immunology meets oncology (TIMO) XII”, April 28th–30th 2016, Halle/Saale, Germany
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 10, 2017 Category: Cancer & Oncology Source Type: research