The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma
AbstractRenal cell carcinoma (RCC) is one of the most lethal urologic malignancies. Its incidence continues to rise worldwide with a rate of 2% per year. Approximately, one-third of the RCC patients are diagnosed at advanced stages due to the asymptomatic nature of its early stages. This represents a great hurdle, since RCC is largely chemoresistant/radioresistant, and targeted therapy of mRCC still has limited efficacy. The 5-year survival rate of metastatic RCC (mRCC) is only around 10%. Adoptive cell transfer (ACT), a particular form of cell-based anticancer immunotherapy, is a promising approach in the treatment of mRC...
Source: Cancer Immunology, Immunotherapy - June 20, 2019 Category: Cancer & Oncology Source Type: research

Naturally occurring cancers in pet dogs as pre-clinical models for cancer immunotherapy
AbstractDespite the significant progress in tumor prevention, early detection, diagnosis and treatment made over recent decades, cancer is still an enormous public health challenge all around the world, with the number of people affected increasing every year. A great deal of effort is therefore being devoted to the search for novel safe, effective and economically sustainable treatments for the growing population of neoplastic patients. One main obstacle to this process is the extremely low percentage of therapeutic approaches that, after successfully passing pre-clinical testing, actually demonstrate activity when finall...
Source: Cancer Immunology, Immunotherapy - June 20, 2019 Category: Cancer & Oncology Source Type: research

Editing the immunopeptidome of melanoma cells using a potent inhibitor of endoplasmic reticulum aminopeptidase 1 (ERAP1)
AbstractThe efficacy of cancer immunotherapy, including treatment with immune-checkpoint inhibitors, often is limited by ineffective presentation of antigenic peptides that elicit T-cell-mediated anti-tumor cytotoxic responses. Manipulation of antigen presentation pathways is an emerging approach for enhancing the immunogenicity of tumors in immunotherapy settings. ER aminopeptidase 1 (ERAP1) is an intracellular enzyme that trims peptides as part of the system that generates peptides for binding to MHC class I molecules (MHC-I). We hypothesized that pharmacological inhibition of ERAP1 in cells could regulate the cellular i...
Source: Cancer Immunology, Immunotherapy - June 20, 2019 Category: Cancer & Oncology Source Type: research

Preclinical assessment of transiently TCR redirected T cells for solid tumour immunotherapy
AbstractOff-target toxicity due to the expression of target antigens in normal tissue or TCR cross-reactivity represents a major risk when using T cell receptor (TCR)-engineered T cells for treatment of solid tumours. Due to the inherent cross-reactivity of TCRs it is difficult to accurately predict their target recognition pre-clinically. It has become evident that direct testing in a human being represents the best evaluation of the risks. There is, therefore, a clear unmet need for assessing the safety of a therapeutic TCR in a more controllable manner than by the injection of permanently modified cellular products. Usi...
Source: Cancer Immunology, Immunotherapy - June 18, 2019 Category: Cancer & Oncology Source Type: research

Intratumoral plasmacytoid dendritic cells as a poor prognostic factor for hepatocellular carcinoma following curative resection
In conclusion, our study demonstrated that intratumoral infiltration by pDCs is a novel indicator for poor prognosis in patients with HCC, possibly through the induction of an immune tolerogenic and inflammatory tumor microenvironment comprising regulatory T and IL-17-producing cells. An assessment of the combination of these cells represents a superior predictor of patient outcome. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 14, 2019 Category: Cancer & Oncology Source Type: research

Clinicopathological implications of TIM3 + tumor-infiltrating lymphocytes and the miR-455-5p/Galectin-9 axis in skull base chordoma patients
AbstractChordoma is difficult to eradicate due to high local recurrence rates. The immune microenvironment is closely associated with tumor prognosis; however, its role in skull base chordoma is unknown. The expression of Galectin-9 (Gal9) and tumor-infiltrating lymphocyte (TIL) markers was assessed by immunohistochemistry. Kaplan –Meier and multivariate Cox analyses were used to assessing local recurrence-free survival (LRFS) and overall survival (OS) of patients. MiR-455-5p was identified as a regulator of Gal9 expression. Immunopositivity for Gal9 was associated with tumor invasion (p = 0.019), Karno...
Source: Cancer Immunology, Immunotherapy - June 13, 2019 Category: Cancer & Oncology Source Type: research

Combination of denosumab and immune checkpoint inhibition: experience in 29 patients with metastatic melanoma and bone metastases
ConclusionsThe combination therapy of metastatic melanoma with PD-1i and denosumab was feasible without unexpected safety issues and showed a promising efficacy signal. Further investigation in prospective studies is needed. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 11, 2019 Category: Cancer & Oncology Source Type: research

Comparison of IL-2 vs IL-7/IL-15 for the generation of NY-ESO-1-specific T cells
In conclusion, IL-7/IL-15 does not seem to be superior to IL-2 for the generation of NY-ESO-1-specific T cells. This is in sharp contrast to the observations in CD19-specific CART cells. Changes of cytokine cocktails should be carefully evaluated for individual vector systems. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 8, 2019 Category: Cancer & Oncology Source Type: research

An HER2 DNA vaccine with evolution-selected amino acid substitutions reveals a fundamental principle for cancer vaccine formulation in HER2 transgenic mice
AbstractEnhancement of endogenous immunity to tumor-associated self-antigens and neoantigens is the goal of preventive vaccination. Toward this goal, we compared the efficacy of the following HER2 DNA vaccine constructs: vaccines encoding wild-type HER2, hybrid HER2 vaccines consisting of human HER2 and rat Neu, HER2 vaccines with single residue substitutions and a novel human HER2 DNA vaccine, ph(es)E2TM. ph(es)E2TM was designed to contain fiveevolution-selected substitutions: M198V, Q398R, F425L, H473R and A622T that occur frequently in 12 primate HER2 sequences. These ph(es)E2TM substitutions score 0 to 1 in blocks subs...
Source: Cancer Immunology, Immunotherapy - June 8, 2019 Category: Cancer & Oncology Source Type: research

Evaluation of the efficacy of immunotherapy for non-resectable mucosal melanoma
ConclusionIn the patients with unresectable and/or metastatic mucosal melanoma, we found ORR and PFS rates comparable to those in patients with cutaneous melanoma, with no significant differences in the types of mucosal surfaces involved. Anti-PD1 therapy has a more favorable benefit-risk ratio than ipilimumab and should be used preferentially. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 7, 2019 Category: Cancer & Oncology Source Type: research

Pembrolizumab as first-line treatment for metastatic uveal melanoma
ConclusionsThe efficacy of Pembrolizumab does not seem particularly different when compared to other agents for mUM, but responding patients had a remarkable disease control. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 7, 2019 Category: Cancer & Oncology Source Type: research

PLAC1: biology and potential application in cancer immunotherapy
AbstractThe emergence of immunotherapy has revolutionized medical oncology with unprecedented advances in cancer treatment over the past two decades. However, a major obstacle in cancer immunotherapy is identifying appropriate tumor-specific antigens to make targeted therapy achievable with fewer normal cells being impaired. The similarity between placentation and tumor development and growth has inspired many investigators to discover antigens for effective immunotherapy of cancers. Placenta-specific 1 (PLAC1) is one of the recently discovered placental antigens with limited normal tissue expression and fundamental roles ...
Source: Cancer Immunology, Immunotherapy - June 5, 2019 Category: Cancer & Oncology Source Type: research

Inhibition of murine hepatoma tumor growth by cryptotanshinone involves TLR7-dependent activation of macrophages and induction of adaptive antitumor immune defenses
In this study, we investigated whether CT could be used to treat hepatocellular carcinoma (HCC) using a mouse Hepa1-6 model. CT inhibited the proliferation of mouse hepatoma (Hepa1-6) cells in vitro by inducing Hepa1-6 cells apoptosis through the JAK2/STAT3 signaling pathway. In addition, CT activated macrophages and polarized mouse bone marrow-derived macrophages (BMM) toward an M1 phenotype in vitro, which depended on the TLR7/MyD88/NF- κB signaling pathway. Furthermore, CT significantly inhibited the growth of syngeneic Hepa1-6 hepatoma tumors, and, in combination with anti-PD-L1 cured Hepa1-6-bearing mice with th...
Source: Cancer Immunology, Immunotherapy - June 3, 2019 Category: Cancer & Oncology Source Type: research

Impact of combination immunochemotherapies on progression of 4NQO-induced murine oral squamous cell carcinoma
AbstractAdvanced oral squamous cell carcinomas (OSCC) have limited therapeutic options. Although immune therapies are emerging as a potentially effective alternative or adjunct to chemotherapies, the therapeutic efficacy of combination immune chemotherapies has yet to be determined. Using a 4-nitroquinolone-N-oxide (4NQO) orthotopic model of OSCC in immunocompetent mice, we evaluated the therapeutic efficacy of single- and combined-agent treatment with a poly-epitope tumor peptide vaccine, cisplatin and/or an A2AR inhibitor, ZM241385. The monotherapies or their combinations resulted in a partial inhibition of tumor growth ...
Source: Cancer Immunology, Immunotherapy - May 28, 2019 Category: Cancer & Oncology Source Type: research

Patterns of immune-cell infiltration in murine models of melanoma: roles of antigen and tissue site in creating inflamed tumors
AbstractImmune-cell infiltration is associated with improved survival in melanoma. Human melanoma metastases may be grouped into immunotypes representing patterns of immune-cell infiltration: A (sparse), B (perivascular cuffing), and C (diffuse). Immunotypes have not been defined for murine melanomas, but may provide opportunities to understand mechanism-driving immunotype differences. We performed immunohistochemistry with immune-cell enumeration, immunotyping, and vascular density scoring in genetically engineered (Braf/Pten and Braf/Pten/ β-catenin) and transplantable (B16-F1, B16-OVA, and B16-AAD) murine melanomas...
Source: Cancer Immunology, Immunotherapy - May 27, 2019 Category: Cancer & Oncology Source Type: research

Metabolic remodeling contributes towards an immune-suppressive phenotype in glioblastoma
AbstractGlioblastoma (GBM) is one of the most aggressive tumors. Numerous studies in the field of immunotherapy have focused their efforts on identifying various pathways linked with tumor-induced immunosuppression. Recent research has demonstrated that metabolic reprogramming in a tumor can contribute towards immune tolerance. To begin to understand the interface between metabolic remodeling and the immune-suppressive state in GBM, we performed a focused, integrative analysis coupling metabolomics with gene-expression profiling in patient-derived GBM (n = 80) and compared them to low-grade astrocytoma (LGA;n...
Source: Cancer Immunology, Immunotherapy - May 22, 2019 Category: Cancer & Oncology Source Type: research

Checkpoint blockade immunotherapy enhances the frequency and effector function of murine tumor-infiltrating T cells but does not alter TCR β diversity
AbstractCheckpoint blockade immunotherapy is now a first-line treatment option for patients with melanoma. Despite achieving objective responses in about half of patients, the exact immune mechanisms elicited and those required for therapeutic success have not been clearly identified. Insight into these mechanisms is key for improving outcomes in a broader range of cancer patients. We used a murine melanoma model to track responses by different subsets of tumor-infiltrating lymphocytes (TIL) during checkpoint blockade immunotherapy. Tumors from treated mice had increased frequencies of both CD4+ and CD8+ T cells, which als...
Source: Cancer Immunology, Immunotherapy - May 18, 2019 Category: Cancer & Oncology Source Type: research

Novel circulating tumor cell-based blood test for the assessment of PD-L1 protein expression in treatment-na ïve, newly diagnosed patients with non-small cell lung cancer
AbstractWe evaluated the analytical and clinical performance of a novel circulating tumor cell (CTC)-based blood test for determination of programmed death ligand 1 (PD-L1) protein expression status in real time in treatment-na ïve non-small cell lung cancer (NSCLC) patients. CTCs were detected in 86% of patients with NSCLC (I–IV) at the time of diagnosis, with a 67% PD-L1 positivity rate (≥ 1 PDL + CTC). Among 33 NSCLC patients with PD-L1 results available via both tissue immunohistochemistry (IHC) and CTC assa ys, 78.9% were positive according to both methods. The CTC test identified an...
Source: Cancer Immunology, Immunotherapy - May 14, 2019 Category: Cancer & Oncology Source Type: research

First-in-human phase 1 dose-escalating trial of G305 in patients with advanced solid tumors expressing NY-ESO-1
AbstractHuman tumor cells express antigens that serve as targets for the host cellular immune system. This phase 1 dose-escalating study was conducted to assess safety and tolerability of G305, a recombinant NY-ESO-1 protein vaccine mixed with glucopyranosyl lipid A (GLA), a synthetic TLR4 agonist adjuvant, in a stable emulsion (SE). Twelve patients with solid tumors expressing NY-ESO-1 were treated using a 3  + 3 design. The NY-ESO-1 dose was fixed at 250 µg, while GLA-SE was increased from 2 to 10 µg. Safety, immunogenicity, and clinical responses were assessed prior to, during, and at...
Source: Cancer Immunology, Immunotherapy - May 8, 2019 Category: Cancer & Oncology Source Type: research

Characterization of circulating T-, NK-, and NKT cell subsets in patients with colorectal cancer: the peripheral blood immune cell profile
ConclusionThe altered phenotype of circulating immune cell subsets in CRC and its association with clinical outcome highlight the potential use of PBMC subsets as prognostic biomarkers in CRC, thereby contributing to better insight into the role of systemic immune profiles in tumor progression. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 3, 2019 Category: Cancer & Oncology Source Type: research

Systemic and local immunosuppression in patients with high-grade meningiomas
ConclusionsPatients with meningiomas exhibit signs of peripheral immunosuppression, including increased PD-L1 on myeloid cells and elevated MDSC abundance proportional to tumor grade. Additionally, the tumors express substantial PD-L1 proportional to tumor grade. These results suggest a role for immune checkpoint inhibitors targeting the PD-L1/PD-1 pathway in combination with standard therapies for the treatment of high-grade meningiomas. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 27, 2019 Category: Cancer & Oncology Source Type: research

Age and sex have no impact on expression levels of markers of immune cell infiltration and immune checkpoint pathways in patients with muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy
ConclusionsThe association between advanced age, female sex, and worse outcomes in bladder cancer may be independent of the immune pathways active in the disease that we examined in this study. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 17, 2019 Category: Cancer & Oncology Source Type: research

MHC class-I downregulation in PD-1/PD-L1 inhibitor refractory Merkel cell carcinoma and its potential reversal by histone deacetylase inhibition: a case series
We report four cases of patients with metastatic MCC who did not respond to immunotherapy by PD-1/PD-L1 blockade. Two of the patients received, subsequently, the HDACi panobinostat in combination with PD-1/PD-L1 blockade. Tumor biopsies of the patients were analyzed for cellular and molecular markers of antigen processing and presentation as well as the degree of T-cell infiltration.Results and conclusionLow expression of APM-related genes associated with low HLA class-I surface expression was observed in all MCC patients, progressing on PD-1/PD-L1 blockade. In one evaluable patient, of the two treated with the combination...
Source: Cancer Immunology, Immunotherapy - April 16, 2019 Category: Cancer & Oncology Source Type: research

Cryptotanshinone has curative dual anti-proliferative and immunotherapeutic effects on mouse Lewis lung carcinoma
AbstractLung cancer is currently the leading cause of cancer-related mortality with very limited effective therapy. Screening of a variety of traditional Chinese medicines (TCMs) for their capacity to inhibit the proliferation of human lung cancer A549 cells and to induce the in vitro maturation of human DCs led to the identification of cryptotanshinone (CT), a compound purified from the TCMSalvia miltiorrhiza Bunge. Here, CT was shown to inhibit the proliferation of mouse Lewis lung carcinoma (LLC) cells by upregulating p53, downregulating cyclin B1 and Cdc2, and, consequently, inducing G2/M cell-cycle arrest of LLC cells...
Source: Cancer Immunology, Immunotherapy - April 10, 2019 Category: Cancer & Oncology Source Type: research

Immune-phenotyping of pleomorphic dermal sarcomas suggests this entity as a potential candidate for immunotherapy
ConclusionsTogether, we provide first explorative evidence about the immune-environment of PDS tumors that may guide future decisions whether individuals presenting with advanced PDS could qualify for immunotherapeutic options. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 8, 2019 Category: Cancer & Oncology Source Type: research

Sirtuin2 enhances the tumoricidal function of liver natural killer cells in a mouse hepatocellular carcinoma model
In this study, we used a chemical-induced mouse HCC model to identify the upregulation of Sirtuin2 (SIRT2) in liver NK cells. In particular, SIRT2 was predominantly expressed in liver CD94+ NK cells. The HCC liver microenvironment induced SIRT2 expression in NK cells. In addition, overexpression of exogenous SIRT2 significantly upregulated the production of cytokines and cytotoxic mediators in activated NK cells. Consistently, SIRT2-overexpressing NK cells showed a stronger tumoricidal effect on hepatoma cells. Moreover, SIRT2 remarkably promoted the phosphorylation of Extracellular-signal-regulated kinase 1/2 (Erk1/2) and...
Source: Cancer Immunology, Immunotherapy - April 6, 2019 Category: Cancer & Oncology Source Type: research

T-cell recognition of non-mutated tumor antigens in healthy individuals: connecting endogenous immunity and tumor dormancy
AbstractThe concept of a dual functional programme of the immune system to destroy malignant cells but also to edit their immunogenic profile, considerably improved our understanding of the process of tumor evolution in the context of a continuum of interactions between tumor cells and immune lymphocytes. Such an endogenous antitumor immunity throughout the period of cancer development established the concept of cancer immunomodulation which is practically based on a process of selection of more clonal tumors which are manageable by the immune system and constitute the equilibrium phase of immunoediting. The duration of th...
Source: Cancer Immunology, Immunotherapy - April 6, 2019 Category: Cancer & Oncology Source Type: research

Expression profiling of immune inhibitory Siglecs and their ligands in patients with glioma
In conclusion, our data show a distinct Siglec expression profile for M- and PMN-MDSCs and propose possible sialic acid –Siglec interactions between glioma cells and MDSCs in the tumor microenvironment. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 5, 2019 Category: Cancer & Oncology Source Type: research

Heterogeneity of PD-L1 expression and CD8 tumor-infiltrating lymphocytes among subtypes of cutaneous adnexal carcinomas
AbstractBackgroundAdnexal carcinomas are rare and heterogeneous skin tumors, for which no standard treatments exist for locally advanced or metastatic tumors.Aim of the studyTo evaluate the expression of PD-L1 and CD8 in adnexal carcinomas, and to study the association between PD-L1 expression, intra-tumoral T cell CD8+ infiltrate, and metastatic evolution.Materials and methodsEighty-three adnexal carcinomas were included. Immunohistochemistry using anti-PD-L1 monoclonal antibodies (E1L3N and 22C3) and CD8 was performed. PD-L1 expression in tumor and immune cells, and CD8+ tumor-infiltrating lymphocyte (TIL) density were a...
Source: Cancer Immunology, Immunotherapy - April 5, 2019 Category: Cancer & Oncology Source Type: research

Modulation of NK cells with checkpoint inhibitors in the context of cancer immunotherapy
AbstractThe incidence of some types of tumours has increased progressively in recent years and is expected to continue growing in the coming years due in part to the aging of the population. The design of new therapies based on natural killer (NK) cells opens new possibilities especially for the treatment of elderly patients who are particularly susceptible to the toxicity of conventional chemotherapy treatments. In recent years, the potential use of NK cells in cancer immunotherapy has been of great interest thanks to advances in the study of NK cell biology. The identification of key points (checkpoints) in the activatio...
Source: Cancer Immunology, Immunotherapy - April 5, 2019 Category: Cancer & Oncology Source Type: research

“Tumor Immunology Meets Oncology (TIMO) XIV”, May 24–26th 2018, Halle/Saale, Germany
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 4, 2019 Category: Cancer & Oncology Source Type: research

Unlocking the therapeutic potential of primary tumor-draining lymph nodes
AbstractLymph nodes draining the primary tumor are essential for the initiation of an effective anti-tumor T-cell immune response. However, cancer-derived immune suppressive factors render the tumor-draining lymph nodes (TDLN) immune compromised, enabling tumors to invade and metastasize. Unraveling the different mechanisms underlying this immune escape will inform therapeutic intervention strategies to halt tumor spread in early clinical stages. Here, we review our findings from translational studies in melanoma, breast, and cervical cancer and discuss clinical opportunities for local immune modulation of TDLN in each of ...
Source: Cancer Immunology, Immunotherapy - April 3, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Autologous tumor cell vaccination combined with systemic CpG-B and IFN- α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial
In the original publication of the article the following abstract and keywords  were inadvertently omitted. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 27, 2019 Category: Cancer & Oncology Source Type: research

The role of immune infiltrates as prognostic biomarkers in patients with breast cancer
AbstractThe presence of immune infiltrates in the tumor microenvironment has been documented in many types of cancer. Moreover, the preexistent or endogenous immunity which consists of interactions between intratumoral lymphocytes and tumor cells is mostly relevant for the successful application of various anticancer therapies, including standard chemotherapy, immune checkpoint inhibition-based immunotherapy and targeted therapies. The immunoscore defines densities of intratumoral immune infiltrates which determine poor or favorable prognosis depending on their quantity and quality in the tumor compartments. Results from l...
Source: Cancer Immunology, Immunotherapy - March 23, 2019 Category: Cancer & Oncology Source Type: research

MDSC and beyond: a symposium-in-writing on myeloid cells with immunoregulatory activity by members of the Mye-EUNITER network
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 18, 2019 Category: Cancer & Oncology Source Type: research

An immunosuppressive macrophage profile attenuates the prognostic impact of CD20-positive B cells in human soft tissue sarcoma
ConclusionsAnalysis of CD20/MS4A1 expression in soft tissue sarcoma merits further attention as a promising candidate prognostic tool for survival, but not in patients with a pronounced immunosuppressive tumor microenvironment. Macrophages are ubiquitous and polarized toward a protumoral phenotype. This provides a rationale for further studies on B cell function and immunotherapy targeting M2-polarized macrophages. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 16, 2019 Category: Cancer & Oncology Source Type: research

Pre-existing autoimmune disease and the risk of immune-related adverse events among patients receiving checkpoint inhibitors for cancer
ConclusionPre-existing autoimmune disease was not associated with time to any hospitalization after initiating ICI therapy, but it was associated with a modest increase in hospitalizations with irAE diagnoses and with corticosteroid treatment. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 15, 2019 Category: Cancer & Oncology Source Type: research

DNA lesions correlate with lymphocyte function after selective internal radiotherapy
AbstractIn patients with non-resectable hepatic malignancies selective internal radiotherapy (SIRT) with yttrium-90 is an effective therapy. However, previous data indicate that SIRT leads to impaired immune function. The aim of the current study was to determine the extent of DNA lesions in peripheral blood mononuclear cells of SIRT patients and to correlate these lesions with cellular immune responses. In ten patients γH2AX and 53BP1 foci were determined. These foci are markers of DNA double-strand breaks (DSBs) and occur consecutively. In parallel, lymphocyte proliferation was assessed after stimulation with the T...
Source: Cancer Immunology, Immunotherapy - March 15, 2019 Category: Cancer & Oncology Source Type: research

Acknowledgements
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 15, 2019 Category: Cancer & Oncology Source Type: research

Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition
AbstractImmune-checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however,>  60% of treated patients do not respond to ICI. Current biomarkers do not reliably explain ICI resistance. Given the link between ICI and autoimmunity, we investigated if genetic susceptibility to autoimmunity modulates ICI efficacy. In 436 patients with metastatic melanoma receiving single line I CI or combination treatment, we tested 25 SNPs, associated with>  2 autoimmune diseases in recent genome-wide association studies, for modulation of ICI efficacy. We found that rs17388568—a risk vari...
Source: Cancer Immunology, Immunotherapy - March 12, 2019 Category: Cancer & Oncology Source Type: research

Autologous tumor cell vaccination combined with systemic CpG-B and IFN- α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 9, 2019 Category: Cancer & Oncology Source Type: research

HCT-116 colorectal cancer cells secrete chemokines which induce chemoattraction and intracellular calcium mobilization in NK92 cells
AbstractWe recently reported that pretreatment of IL-2 activated human natural killer (NK) cells with the drugs dimethyl fumarate (DMF) and monomethyl fumarate (MMF) upregulated the expression of surface chemokine receptor CCR10. Ligands for CCR10, namely CCL27 and CCL28, induced the chemotaxis of these cells. Here, we performed a bioinformatics analysis to see which chemokines might be expressed by the human HCT-116 colorectal cancer cells. We observed that, in addition to CCL27 and CCL28, HCT-116 colorectal cancer cells profoundly express CXCL16 which binds CXCR6. Consequently, NK92 cells were treated with DMF and MMF fo...
Source: Cancer Immunology, Immunotherapy - March 7, 2019 Category: Cancer & Oncology Source Type: research

Absolute numbers of regulatory T cells and neutrophils in corticosteroid-free patients are predictive for response to bevacizumab in recurrent glioblastoma patients
AbstractBevacizumab (Bv) remains frequently prescribed in glioblastoma (GBM) patients, especially at recurrence. We conducted a prospective clinical trial with 29 recurrent GBM patients treated with Bv alone with a longitudinal follow-up of different circulating immune cells [complete blood count, myeloid-derived suppressor cells (MDSCs), classical, intermediate, non-classical and Tie2 monocytes, VEGFR1+ and regulatory T cells (Treg)]. We observed a significant increase for leucocytes, neutrophils, eosinophils and classical monocytes and a decrease for the fraction of Treg during the treatment. The best prognostic values f...
Source: Cancer Immunology, Immunotherapy - March 4, 2019 Category: Cancer & Oncology Source Type: research

Expression of a soluble IL-10 receptor enhances the therapeutic effects of a papillomavirus-associated antitumor vaccine in a murine model
In conclusion, the proposed treatment involving the expression of IL-10R enhanced the antitumor protective immunity induced by pgDE7h administration and may contribute to the development of more efficient clinical interventions against HPV-induced tumors. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 26, 2019 Category: Cancer & Oncology Source Type: research

First-line therapy-stratified survival in BRAF-mutant melanoma: a retrospective multicenter analysis
ConclusionFirst-line treatment with a PD-1 blocking antibody might be associated with longer OS than first-line inhibition of the MAPK pathway in patients with advanced melanoma harboring mutant BRAF. These hypothesis-generating data need to be confirmed or rejected in prospective, randomized trials. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 26, 2019 Category: Cancer & Oncology Source Type: research

Melanoma-associated antigen-A and programmed death-ligand 1 expression are associated with advanced urothelial carcinoma
ConclusionMAGE-A and PD-L1 expression is increased in advanced disease and associated with shorter PFS. Furthermore, MAGE-A expression was significantly associated with higher-grade and -stage disease and associated with shorter RFS and PFS. The worse prognosis associated with MAGE-A+/PD-L1+  provides evidence that a combinatorial treatment strategy co-targeting MAGE/PD-L1 might be feasible. Further studies are needed to validate these findings. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 21, 2019 Category: Cancer & Oncology Source Type: research

Natural T cell autoreactivity to melanoma antigens: clonally expanded melanoma-antigen specific CD8  + memory T cells can be detected in healthy humans
AbstractWe used four-color ImmunoSpot ® assays, in conjunction with peptide pools that cover the sequence of tyrosinase (Tyr), melanoma-associated antigen A3 (MAGE-A3), melanocyte antigen/melanoma antigen recognized by T cells 1 (Melan-A/MART-1), glycoprotein 100 (gp100), and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) to characterize the melanoma antigen (MA)-specific CD8 + cell repertoire in PBMC of 40 healthy human donors (HD). Tyr triggered interferon gamma (IFN-γ)-secreting CD8 + T cells in 25% of HD within 24 h of antigen stimulation ex vivo. MAGE-A3, Melan-A/MA...
Source: Cancer Immunology, Immunotherapy - February 19, 2019 Category: Cancer & Oncology Source Type: research

A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer
AbstractCV9201 is an RNActive®-based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal CV9201 injections (400–1600 µg of mRNA). The primary objective of the trial was to assess safety. Secondary objectives included assessment of antibody and ex vivo...
Source: Cancer Immunology, Immunotherapy - February 15, 2019 Category: Cancer & Oncology Source Type: research

Tumor infiltrating mast cells determine oncogenic HIF-2 α-conferred immune evasion in clear cell renal cell carcinoma
AbstractPurposeHypoxia-inducible factor 2 α (HIF-2α) overexpression leads to activation of angiogenic pathways. However, little is known about the association between HIF-2α expression and anti-tumor immunity in clear cell renal cell carcinoma (ccRCC). We aimed to explore how HIF-2α influenced the microenvironment and the underlying mec hanisms.Experimental designWe immunohistochemically evaluated immune cells infiltrations and prognostic value of HIF-2 α expression in a retrospective Zhongshan Hospital cohort of 280 ccRCC patients. Fresh tumor samples, non-tumor tissues and autologous periphe...
Source: Cancer Immunology, Immunotherapy - February 13, 2019 Category: Cancer & Oncology Source Type: research

Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2
This study shows that this protocol of low-dose IL-2 following adoptive cell transfer of TIL is feasible and clinically active. (ClinicalTrials.gov identifier NCT01883323.) (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 11, 2019 Category: Cancer & Oncology Source Type: research