Surgical trauma induces postoperative T-cell dysfunction in lung cancer patients through the programmed death-1 pathway
Abstract The programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) pathway have been shown to be involved in tumor-induced and sepsis-induced immunosuppression. However, whether this pathway is involved in the surgery-induced dysfunction of T lymphocytes is not known. Here, we analyzed expression of PD-1 and PD-L1 on human peripheral mononuclear cells during the perioperative period. We found that surgery increased PD-1/PD-L1 expression on immune cells, which was correlated with the severity of surgical trauma. The count of T lymphocytes and natural killer cells reduced after surgery, probably due to the...
Source: Cancer Immunology, Immunotherapy - July 17, 2015 Category: Cancer & Oncology Source Type: research

T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response
Abstract Endogenous tumor-specific T cells are detectable in patients with different tumor types including malignant melanoma (MM). They can control tumor growth, have impact on patient survival and correlate with improved clinical response to immune checkpoint therapy. Thus, they may represent a potent biomarker for respective treatment decisions. So far, major target antigens of endogenous MM-reactive T cells have not been determined systematically. Instead, autoantibodies are discussed as surrogate parameter for MM-specific T cells. Throughout a period of more than 60 days after tumor resection, we therefo...
Source: Cancer Immunology, Immunotherapy - July 10, 2015 Category: Cancer & Oncology Source Type: research

Immunotherapy of HPV-associated cancer: DNA/plant-derived vaccines and new orthotopic mouse models
Abstract Under the optimistic assumption of high-prophylactic HPV vaccine coverage, a significant reduction of cancer incidence can only be expected after decades. Thus, immune therapeutic strategies are needed for persistently infected individuals who do not benefit from the prophylactic vaccines. However, the therapeutic strategies inducing immunity to the E6 and/or E7 oncoprotein of HPV16 are more effective for curing HPV-expressing tumours in animal models than for treating human cancers. New strategies/technologies have been developed to improve these therapeutic vaccines. Our studies focussed on preparing th...
Source: Cancer Immunology, Immunotherapy - July 3, 2015 Category: Cancer & Oncology Source Type: research

Hepatic myeloid-derived suppressor cells in cancer
Abstract Myeloid-derived suppressor cells are key components of tumor-induced immune suppression. They are composed of a heterogeneous population of immature myeloid cells that abrogates innate and adaptive immune responses. Myeloid-derived suppressor cells accumulate not only in peripheral blood, secondary lymphoid organs and tumors, but also in the liver in preclinical tumor models and in hepatocellular carcinoma patients. The liver, continuously exposed to food and microbial antigens from the intestine, avoids autoimmune damage through the use of specialized mechanisms of immune tolerance. In the context of...
Source: Cancer Immunology, Immunotherapy - July 2, 2015 Category: Cancer & Oncology Source Type: research

Monitoring regulatory T cells in clinical samples: consensus on an essential marker set and gating strategy for regulatory T cell analysis by flow cytometry
In conclusion, we propose an essential marker set comprising antibodies to CD3, CD4, CD25, CD127, Foxp3, Ki67, and CD45RA and a corresponding robust gating strategy for the context-dependent analysis of Tregs by flow cytometry. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 28, 2015 Category: Cancer & Oncology Source Type: research

Expansion of myeloid-derived suppressor cells in chronic obstructive pulmonary disease and lung cancer: potential link between inflammation and cancer
Conclusions These results suggest that tumor immunosurveillance might be impaired in COPD and may contribute to the increased risk of LC reported in these patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 28, 2015 Category: Cancer & Oncology Source Type: research

A phase I trial combining decitabine/dendritic cell vaccine targeting MAGE-A1, MAGE-A3 and NY-ESO-1 for children with relapsed or therapy-refractory neuroblastoma and sarcoma
Abstract Antigen-specific immunotherapy was studied in a multi-institutional phase 1/2 study by combining decitabine (DAC) followed by an autologous dendritic cell (DC)/MAGE-A1, MAGE-A3 and NY-ESO-1 peptide vaccine in children with relapsed/refractory solid tumors. Patients aged 2.5–15 years with relapsed neuroblastoma, Ewing’s sarcoma, osteosarcoma and rhabdomyosarcoma were eligible to receive DAC followed by DC pulsed with overlapping peptides derived from full-length MAGE-A1, MAGE-A3 and NY-ESO-1. The primary endpoints were to assess the feasibility and tolerability of this regimen. Each of...
Source: Cancer Immunology, Immunotherapy - June 24, 2015 Category: Cancer & Oncology Source Type: research

Sunitinib pretreatment improves tumor-infiltrating lymphocyte expansion by reduction in intratumoral content of myeloid-derived suppressor cells in human renal cell carcinoma
Abstract Targeted therapy with sunitinib, pazopanib or everolimus has improved treatment outcome for patients with metastatic renal cell carcinoma patients (RCC). However, despite considerable efforts in sequential or combined modalities, durable remissions are rare. Immunotherapy like cytokine therapy with interleukin-2, T cell checkpoint blockade or adoptive T cell therapies can achieve long-term benefit and even cure. This raises the question of whether combining targeted therapy with immunotherapy could also be an effective treatment option for RCC patients. Sunitinib, one of the most frequently administered t...
Source: Cancer Immunology, Immunotherapy - June 24, 2015 Category: Cancer & Oncology Source Type: research

Developments in cancer vaccines for hepatocellular carcinoma
Abstract Hepatocellular carcinoma (HCC) accounts for about 6 % of all new cancers diagnosed worldwide and represents one of the leading causes of cancer-related death globally in men and women, respectively. The overall prognosis for HCC patients is poor, especially in the majority of patients with more advanced stage of disease. Indeed, in such cases immunotherapeutic strategies may represent a novel and effective tool. A few immunotherapy trials conducted for HCC have provided divergent results, urging the scientific community to explore additional paths to improve efficacy of immunotherapeutic approach...
Source: Cancer Immunology, Immunotherapy - June 21, 2015 Category: Cancer & Oncology Source Type: research

TLR7 tolerance is independent of the type I IFN pathway and leads to loss of anti-tumor efficacy in mice
Abstract Systemic administration of small molecule toll-like receptor (TLR)-7 agonists leads to potent activation of innate immunity and to the generation of anti-tumor immune responses. However, activation of TLRs with small molecule agonists may lead to the induction of TLR tolerance, defined as a state of hyporesponsiveness to subsequent agonism, which may limit immune activation, the generation of anti-tumor responses and clinical response. Our data reveal that dose scheduling impacts on the efficacy of systemic therapy with the selective TLR7 agonist, 6-amino-2-(butylamino)-9-((6-(2-(dimethylamino)ethoxy)pyri...
Source: Cancer Immunology, Immunotherapy - June 20, 2015 Category: Cancer & Oncology Source Type: research

Targeting of MYCN by means of DNA vaccination is effective against neuroblastoma in mice
Abstract The MYCN oncogene is a strong genetic marker associated with poor prognosis in neuroblastoma (NB). Therefore, MYCN gene amplification and subsequent overexpression provide a possible target for new treatment approaches in NB. We first identified an inverse correlation of MYCN expression with CD45 mRNA in 101 NB tumor samples. KEGG mapping further revealed that MYCN expression was associated with immune-suppressive pathways characterized by a down-regulation of T cell activation and up-regulation of T cell inhibitory gene transcripts. We then aimed to investigate whether DNA vaccination against MYCN is eff...
Source: Cancer Immunology, Immunotherapy - June 16, 2015 Category: Cancer & Oncology Source Type: research

Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas
Conclusion Our data show that immune markers including TILs and CD2 count correlate more closely with survival in ulcerated melanomas than that in non-ulcerated melanomas. We propose that immune biomarkers may be particularly relevant to ulcerated, as compared to non-ulcerated, melanomas and that this merits study in larger populations. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 16, 2015 Category: Cancer & Oncology Source Type: research

Second meeting of the Spanish Immunotherapy Group GEIT (Grupo Español de Inmunoterapia), January 16, 2015, in Zaragoza, Spain
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 16, 2015 Category: Cancer & Oncology Source Type: research

Inhibition of tumor progression during allergic airway inflammation in a murine model: significant role of TGF-β
Conclusion This study is the first to establish an inverse relationship between allergic airway inflammation and tumor progression. This effect appears to be mediated by TGF-β, which is overexpressed in tumor cells during pulmonary allergic inflammation. This study indicates that TGF-β is a potential target for antitumor therapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 16, 2015 Category: Cancer & Oncology Source Type: research

Electrochemotherapy of tumors as in situ vaccination boosted by immunogene electrotransfer
Abstract Electroporation is a platform technology for drug and gene delivery. When applied to cell in vitro or tissues in vivo, it leads to an increase in membrane permeability for molecules which otherwise cannot enter the cell (e.g., siRNA, plasmid DNA, and some chemotherapeutic drugs). The therapeutic effectiveness of delivered chemotherapeutics or nucleic acids depends greatly on their successful and efficient delivery to the target tissue. Therefore, the understanding of different principles of drug and gene delivery is necessary and needs to be taken into account according to the specificity of their deliver...
Source: Cancer Immunology, Immunotherapy - June 12, 2015 Category: Cancer & Oncology Source Type: research

Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies?
Abstract Several age-associated changes in natural killer (NK) cell phenotype have been reported that contribute to the defective NK cell response observed in elderly patients. A remodelling of the NK cell compartment occurs in the elderly with a reduction in the output of immature CD56bright cells and an accumulation of highly differentiated CD56dim NK cells. Acute myeloid leukaemia (AML) is generally a disease of older adults. NK cells in AML patients show diminished expression of several activating receptors that contribute to impaired NK cell function and, in consequence, to AML blast escape from NK cell immun...
Source: Cancer Immunology, Immunotherapy - June 10, 2015 Category: Cancer & Oncology Source Type: research

Intratumoral immunotherapy for melanoma
Abstract Selection of suitable tumor-associated antigens is a major challenge in the development of effective cancer vaccines. Intratumoral (i.t.) immunotherapy empowers the immune system to mount T cell responses against tumor-associated antigens which are most immunogenic. To mediate systemic tumor regression, i.t. immunotherapy must generate systemic T cell responses that can target distant metastases beyond the initially treated tumor mass. Now that promising preclinical results and some initial success in clinical trials have been obtained, we here review i.t. immunotherapy-related preclinical and clinical st...
Source: Cancer Immunology, Immunotherapy - June 7, 2015 Category: Cancer & Oncology Source Type: research

Preferential expansion of pro-inflammatory Tregs in human non-small cell lung cancer
This study aimed to determine Treg subset distributions and characteristics present in non-small cell lung cancer (NSCLC) patients. Methods Peripheral blood was collected from healthy controls (HC) and NSCLC patients preceding surgical resection, and mononuclear cells were isolated, stained, and analyzed by flow cytometry. Tregs were defined by expression of CD4 and CD25 and classified into CD45RA+Foxp3int (naïve, Fr. I) or CD45RA−Foxp3hi (activated Fr. II). Activated conventional T cells were CD4+CD45RA−Foxp3int (Fr. III). Results ...
Source: Cancer Immunology, Immunotherapy - June 6, 2015 Category: Cancer & Oncology Source Type: research

Adoptive immunotherapy of cancer utilizing genetically engineered lymphocytes
Abstract It is becoming increasingly clear that adoptive immunotherapy with genetically engineered T cells has the potential to control and even cure cancer in some patients. On the other hand, severe adverse events associated with efficacy have frequently been reported in clinical trials. Current and near-future challenges for the development of adoptive immunotherapy of cancer using genetically engineered T cells include minimization and prediction of adverse events; identification of new and effective targets, including patient-specific mutations; improvement in T cell functionality, persistence, and memory for...
Source: Cancer Immunology, Immunotherapy - June 4, 2015 Category: Cancer & Oncology Source Type: research

The TLR-2/TLR-6 agonist macrophage-activating lipopeptide-2 augments human NK cell cytotoxicity when PGE2 production by monocytes is inhibited by a COX-2 blocker
Abstract Macrophage-activating lipopeptide-2 (MALP-2) is a potent inducer of proinflammatory cytokine secretion by macrophages, monocytes, and dendritic cells. MALP-2 was reported to be involved in natural killer (NK) cell activation and ensuing tumor rejection. However, the mechanism of MALP-2-mediated NK cell activation remained unclear. Therefore, we studied the effects of MALP-2 on cultured human NK cells. We found that MALP-2 had no direct effect on NK cells. Instead, MALP-2 acted on monocytes and triggered the release of different molecules such as interleukin (IL)-1β, IL-6, IL-10, IL-12, IL-15, interfe...
Source: Cancer Immunology, Immunotherapy - June 3, 2015 Category: Cancer & Oncology Source Type: research

Modulating the innate immune activity in murine tumor microenvironment by a combination of inducer molecules attached to microparticles
Abstract Targeted cancer immunotherapy is challenging due to the cellular diversity and imposed immune tolerance in the tumor microenvironment (TME). A promising route to overcome those drawbacks may be by activating innate immune cells (IIC) in the TME, toward tumor destruction. Studies have shown the ability to “re-educate” pro-tumor-activated IIC toward antitumor responses. The current research aims to stimulate such activation using a combination of innate activators loaded onto microparticles (MP). Four inducers of Toll-like receptors 4 and 7, complement C5a receptor (C5aR) and gamma Fc receptor a...
Source: Cancer Immunology, Immunotherapy - June 2, 2015 Category: Cancer & Oncology Source Type: research

Phase I trial of thymidylate synthase poly-epitope peptide (TSPP) vaccine in advanced cancer patients
Abstract Thymidylate synthase (TS) poly-epitope peptide (TSPP) is a 27-mer peptide vaccine containing the amino acidic sequences of three epitopes with HLA-A2.1-binding motifs of TS, an enzyme overexpressed in cancer cells, which plays a crucial role in DNA repair and replication. Based on the results of preclinical studies, we designed a phase Ib trial (TSPP/VAC1) to investigate, in a dose escalation setting, the safety and the biological activity of TSPP vaccination alone (arm A) or in combination with GM-CSF and IL-2 (arm B) in cancer patients. Twenty-one pretreated metastatic cancer patients, with a good perfo...
Source: Cancer Immunology, Immunotherapy - June 2, 2015 Category: Cancer & Oncology Source Type: research

Genetic susceptibility to cervical squamous cell carcinoma is associated with HLA-DPB1 polymorphisms in Taiwanese women
Abstract Cervical cancer is a multifactorial disease, and increasing evidence suggests that host immunogenetic background may contribute to its pathogenesis. Genetic variations in human leukocyte antigen (HLA) genes may alter the efficiency of immune response to human papillomavirus (HPV) antigens and have been implicated in the risk of cervical cancer. We investigated whether polymorphisms in the HLA-DPB1 gene were associated with cervical cancer risk in a Taiwanese population. HLA-DPB1 alleles and +550 G/A polymorphism were genotyped in a case–control study of 473 women with cervical squamous cell carc...
Source: Cancer Immunology, Immunotherapy - June 2, 2015 Category: Cancer & Oncology Source Type: research

A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit
Abstract Recently, several types of immunotherapies have been shown to induce encouraging clinical results, though in a restricted number of patients. Consequently, there is a need to identify immune biomarkers to select patients who will benefit from such therapies. Such predictive biomarkers may be also used as surrogates for overall survival (OS). We have recently found correlations between immunologic parameters and clinical outcome in prostate cancer patients who had been vaccinated with a HER-2/neu hybrid polypeptide vaccine (AE37) and received one booster 6 months post-primary vaccinations. Herein, we ...
Source: Cancer Immunology, Immunotherapy - May 31, 2015 Category: Cancer & Oncology Source Type: research

Local and systemic XAGE-1b-specific immunity in patients with lung adenocarcinoma
In this study, XAGE-1b expression by tumor cells as well as the presence of systemic and/or local XAGE-1b-specific immunity was assessed in peripheral blood, tumor tissue and tumor-draining lymph nodes of Caucasian patients with pulmonary adenocarcinoma. XAGE-1b protein expression was detected in 43.6 % (17 of 39) of patients when at least two different parts of a resected tumor were assessed. In 20 patients, analysis of T cells isolated and expanded from the primary tumor and its draining lymph node demonstrated XAGE-1b-specific responses in two patients. XAGE-1b-specific immunoglobulin G antibodies were found in 3 o...
Source: Cancer Immunology, Immunotherapy - May 30, 2015 Category: Cancer & Oncology Source Type: research

Targeted treatment of metastatic castration-resistant prostate cancer with sipuleucel-T immunotherapy
Conclusions Sipuleucel-T stimulates long-lived immune responses that translate into long-term clinical benefit. The treatment course (three infusions at weeks 0, 2, and 4) is associated with manageable side effects. Short-term markers of future benefit would be clinically useful, and information on effective treatment combinations or sequences is awaited. Patient summary Sipuleucel-T treatment directs the patient’s own immune system to target and remove prostate cancer cells and increases life expectancy. Patients whose cancer is less advanced generally have a more &l...
Source: Cancer Immunology, Immunotherapy - May 30, 2015 Category: Cancer & Oncology Source Type: research

Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor immune responses in a human MUC1-expressing preclinical ovarian cancer model
Abstract Monoclonal antibodies that block inhibitory immune checkpoint molecules and enhance anti-tumor responses show clinical promise in advanced solid tumors. Most of the preliminary evidence on therapeutic efficacy of immune checkpoint blockers comes from studies in melanoma, lung and renal cancer. To test the in vivo potential of programmed death-ligand 1 (PD-L1) blockade in ovarian cancer, we recently generated a new transplantable tumor model using human mucin 1 (MUC1)-expressing 2F8 cells. The MUC1 transgenic (MUC1.Tg) mice develop large number of intraperitoneal (IP) tumors following IP injection of 8...
Source: Cancer Immunology, Immunotherapy - May 22, 2015 Category: Cancer & Oncology Source Type: research

Orchestrating an immune response against cancer with engineered immune cells expressing αβTCRs, CARs, and innate immune receptors: an immunological and regulatory challenge
Abstract Over half a century ago, the first allogeneic stem cell transplantation (allo-SCT) initiated cellular immunotherapy. For several decades, little progress was made, and toxicity of allo-SCT remained a major challenge. However, recent breakthroughs have opened new avenues to further develop this modality and to provide less toxic and equally efficient interventions for patients suffering from hematological or solid malignancies. Current novel cellular immune interventions include ex vivo expansion and adoptive transfer of tumor-infiltrating immune cells or administration of drugs which antagonize toleri...
Source: Cancer Immunology, Immunotherapy - May 20, 2015 Category: Cancer & Oncology Source Type: research

Phase I/II study of adjuvant immunotherapy with sentinel lymph node T lymphocytes in patients with colorectal cancer
Abstract Although the development of multi-disciplinary management has improved the survival of colorectal cancer (CRC), the prognosis of metastatic CRC patients remains poor. Accumulating evidence has demonstrated that immunotherapy with cancer vaccines and adoptive T cell transfusions may improve outcomes as an adjuvant to current standard CRC treatment. In this phase I/II study, 71 CRC patients who underwent radical surgery (stage I–III, n = 46) or palliative surgery (stage IV with non-resectable synchronous metastases, n = 25) were included. In the first part of this study, sentinel l...
Source: Cancer Immunology, Immunotherapy - May 20, 2015 Category: Cancer & Oncology Source Type: research

Increased CCL17 serum levels are associated with improved survival in advanced melanoma
Conclusion Serum levels of CCL17 and S100B represent independent prognostic markers for melanoma patients with distant metastases. These biomarkers were more powerful than the M category according to the AJCC classification to indicate overall survival. CCL17 represents a promising biomarker upon immune checkpoint blockade in melanoma. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 20, 2015 Category: Cancer & Oncology Source Type: research

STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in melanoma-bearing mice
We report that cyclic diguanylate monophosphate (c-di-GMP), which activates the stimulator of interferon genes, potentiated the immunogenicity and anti-tumor effects of a peptide vaccine against mouse B16 melanoma. The synergistic effects of c-di-GMP required co-administration of costimulatory anti-CD40 antibody, the adjuvant poly-IC, and were mediated in part by IFN-I. These findings demonstrate that peptides representing CD8 T cell epitopes can be effective inducers of large CD8 T cell responses in vaccination strategies that mimic acute viral infections. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 19, 2015 Category: Cancer & Oncology Source Type: research

Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study
We report on the safety and immunogenicity of idiotypic DNA vaccination in a phase I, non-randomised, open-label study in patients with multiple myeloma. The study used DNA fusion gene vaccines encoding patient-specific single chain variable fragment, or idiotype (Id), linked to fragment C (FrC) of tetanus toxin. Patients in complete or partial response following high-dose chemotherapy and autologous stem cell transplant were vaccinated intramuscularly with 1 mg DNA on six occasions, beginning at least 6 months post-transplant; follow-up was to week 52. Fourteen patients were enrolled on study and completed vacci...
Source: Cancer Immunology, Immunotherapy - May 16, 2015 Category: Cancer & Oncology Source Type: research

6-Thioguanine-loaded polymeric micelles deplete myeloid-derived suppressor cells and enhance the efficacy of T cell immunotherapy in tumor-bearing mice
Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that suppress effector T cell responses and can reduce the efficacy of cancer immunotherapies. We previously showed that ultra-small polymer nanoparticles efficiently drain to the lymphatics after intradermal injection and target antigen-presenting cells, including Ly6chi Ly6g− monocytic MDSCs (Mo-MDSCs), in skin-draining lymph nodes (LNs) and spleen. Here, we developed ultra-small polymer micelles loaded with 6-thioguanine (MC-TG), a cytotoxic drug used in the treatment of myelogenous leukemia, with th...
Source: Cancer Immunology, Immunotherapy - May 16, 2015 Category: Cancer & Oncology Source Type: research

Dendritic cells transfected with heat-shock protein 70 messenger RNA for patients with hepatitis C virus-related hepatocellular carcinoma: a phase 1 dose escalation clinical trial
This study demonstrated that HSP70-DCs therapy is both safe and feasible in patients with HCV-related HCC. Further clinical trials should be considered. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 16, 2015 Category: Cancer & Oncology Source Type: research

Intralesional administration of L19-IL2/L19-TNF in stage III or stage IVM1a melanoma patients: results of a phase II study
Abstract The intratumoral injection of cytokines, in particular IL2, has shown promise for cutaneous melanoma patients with unresectable disease or continuous recurrence despite surgery. We recently reported that the intralesional injection of L19-IL2, an immunocytokine combining IL2 and the human monoclonal antibody fragment L19, resulted in efficient regional control of disease progression, increased time to distant metastasis and evidence of effect on circulating immune cell populations. We have also shown in preclinical models of cancer a remarkable synergistic effect of the combination of L19-IL2 with L19...
Source: Cancer Immunology, Immunotherapy - May 14, 2015 Category: Cancer & Oncology Source Type: research

Impact of the immunomodulating peptide thymosin alpha 1 on multiple myeloma and immune recovery after hematopoietic stem cell transplantation
In conclusion, despite direct effects of Tα1 on human MM cell line proliferation in vitro, Tα1 did not exert anti-myeloma effects in vivo in the two murine models tested. Moreover, Tα1 failed to improve immune recovery in a xenogeneic HSCT model. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 14, 2015 Category: Cancer & Oncology Source Type: research

Cytokine production in patients with papillary thyroid cancer and associated autoimmune Hashimoto thyroiditis
In conclusion, autoimmune HT affects the cytokine profile of patients with PTC by stimulating secretion of Th1/Th2/Th9 types of cytokines. Th1/Th2 cytokine ratios in PTC patients with associated autoimmune HT indicate a marked shift toward Th2 immunity. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 14, 2015 Category: Cancer & Oncology Source Type: research

Extended evaluation of a phase 1/2 trial on dosing, safety, immunogenicity, and overall survival after immunizations with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine in late-stage colorectal cancer
We report our extended observations on long-term overall survival and further immune analyses on a subset of treated patients including assessment of cytolytic T cell responses, T regulatory (Treg) to T effector (Teff) cell ratios, flow cytometry on peripheral blood mononuclear cells (PBMCs), and determination of HLA-A2 status. An overall survival of 20 % (median survival 11 months) was observed during long-term follow-up, and no long-term adverse effects were reported. Cytolytic T cell responses increased after immunizations, and cell-mediated immune (CMI) responses were induced whether or not patients were HLA-...
Source: Cancer Immunology, Immunotherapy - May 8, 2015 Category: Cancer & Oncology Source Type: research

CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion
Abstract Background Malignant pleural effusion (MPE) is a common complication caused by malignant diseases. However, subjectivity, poor sensitivity, and substantial false-negative rates of cytology assay hamper accurate MPE diagnosis. The aim of this study was to assess whether CD163+CD14+ tumor-associated macrophages (TAMs) could be used as a biomarker for enabling sensitive and specific MPE diagnosis. Methods Pleural effusion samples and peripheral blood samples were collected from 50 MPE patients and 50 non-malignant pleural effusion (NMPE) patients, ...
Source: Cancer Immunology, Immunotherapy - May 6, 2015 Category: Cancer & Oncology Source Type: research

Novel metronomic chemotherapy and cancer vaccine combinatorial strategy for hepatocellular carcinoma in a mouse model
Abstract Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and represents the third and the fifth leading cause of cancer-related death worldwide in men and women, respectively. Hepatitis B virus (HBV) and hepatitis C virus (HCV) chronic infections account for pathogenesis of more than 80 % of primary HCC. HCC prognosis greatly varies according to stage at beginning of treatment, but the overall 5-year survival rate is approximately 5–6 %. Given the limited number of effective therapeutic strategies available, immunotherapies and therapeutic cancer vaccines may help in im...
Source: Cancer Immunology, Immunotherapy - May 6, 2015 Category: Cancer & Oncology Source Type: research

“Cancer Bio-Immunotherapy in Siena”: Twelfth Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT), Siena, Italy, October 9–11, 2014
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 6, 2015 Category: Cancer & Oncology Source Type: research

Optimal selection of natural killer cells to kill myeloma: the role of HLA-E and NKG2A
Abstract Immunotherapy with allogeneic natural killer (NK) cells offers therapeutic perspectives for multiple myeloma patients. Here, we aimed to refine NK cell therapy by evaluation of the relevance of HLA-class I and HLA-E for NK anti-myeloma reactivity. We show that HLA-class I was strongly expressed on the surface of patient-derived myeloma cells and on myeloma cell lines. HLA-E was highly expressed by primary myeloma cells but only marginally by cell lines. HLA-Elow expression on U266 cells observed in vitro was strongly upregulated after in vivo (bone marrow) growth in RAG-2−/− &gam...
Source: Cancer Immunology, Immunotherapy - April 29, 2015 Category: Cancer & Oncology Source Type: research

Myeloid molecular characteristics of human γδ T cells support their acquisition of tumor antigen-presenting capacity
In this study, we have investigated the molecular characteristics of human γδ T cells related to their acquisition of antigen-presenting capacity in comparison with activated αβ T cells. We found that activated γδ but not αβ T cells upregulated cell surface expression of a scavenger receptor, CD36, which seemed to be mediated by signaling through mitogen-activated protein kinase and/or NF-κB pathways. Confocal microscopical analysis revealed that activated γδ T cells can phagocytose protein antigens. Activated γδ T cells could induce tumor antigen-...
Source: Cancer Immunology, Immunotherapy - April 24, 2015 Category: Cancer & Oncology Source Type: research

Development of a potent melanoma vaccine capable of stimulating CD8 + T-cells independently of dendritic cells in a mouse model
This study shows that the B16-F10-4-1BBL-B7.1-IFNγ/β anticancer vaccine acted as a highly effective antigen-presenting cell and is likely to be able to directly stimulate CD8+ T-cells, without requiring co-stimulatory signals from either CD4+ T-cells or DCs, and warrants translation of this technology into the clinical setting. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 19, 2015 Category: Cancer & Oncology Source Type: research

Immunostimulatory early phenotype of tumor-associated macrophages does not predict tumor growth outcome in an HLA-DR mouse model of prostate cancer
Abstract Tumor-associated macrophages (TAM) were shown to support the progression of many solid tumors. However, anti-tumor properties of TAM were also reported in several types of cancer. Here, we investigated the phenotype and functions of TAM in two transgenic mouse models of prostate cancer that display striking differences in tumor growth outcome. Mice expressing prostate-specific antigen (PSA) as a self-antigen specifically in prostate (PSAtg mice) rejected PSA-expressing transgenic adenocarcinoma of mouse prostate (TRAMP) tumors. However, the introduction of HLA-DRB1*1501 (DR2b) transgene presenting PSA-der...
Source: Cancer Immunology, Immunotherapy - April 19, 2015 Category: Cancer & Oncology Source Type: research

Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis
Abstract To examine the relationship between cytotoxic T lymphocyte antigen 4 (CTLA-4) expression and breast cancer prognosis, CTLA-4 expression was immunohistochemically detected in paraffin-embedded specimens of primary tumors from 130 patients with breast cancer who had a mean follow-up period of 112 months. CTLA-4 expressed in cytoplasm of breast cancer cells and in cytoplasm and cell membranes of interstitial lymphocytes. Univariate analysis (log-rank) associated higher density of interstitial CTLA-4+ lymphocytes with longer DFS and OS, but higher tumor CTLA-4 expression with shorter OS. After controllin...
Source: Cancer Immunology, Immunotherapy - April 17, 2015 Category: Cancer & Oncology Source Type: research

Persistent HPV16/18 infection in Indian women with the A-allele (rs6457617) of HLA-DQB1 and T-allele (rs16944) of IL-1β −511 is associated with development of cervical carcinoma
Abstract The aim of this study was to understand the association of human papillomavirus (HPV) type 16/18 infection and polymorphisms in the HLA-DQB1 (rs6457617) and IL-1β –511 (rs16944) loci with the development of uterine cervical cancer (CaCx). The distribution of HLA-DQB1 G > A and IL-1β −511 C/T polymorphisms was determined in HPV-negative cervical swabs from normal women (N = 111) and compared with cervical swabs of HPV-cleared normal women (once HPV infected followed by natural clearance of the infection, N = 86), HPV16/18-positive cervical intraepi...
Source: Cancer Immunology, Immunotherapy - April 17, 2015 Category: Cancer & Oncology Source Type: research

Engineering monocyte-derived dendritic cells to secrete interferon-α enhances their ability to promote adaptive and innate anti-tumor immune effector functions
Abstract Dendritic cell (DC) vaccination has demonstrated potential in clinical trials as a new effective cancer treatment, but objective and durable clinical responses are confined to a minority of patients. Interferon (IFN)-α, a type-I IFN, can bolster anti-tumor immunity by restoring or increasing the function of DCs, T cells and natural killer (NK) cells. Moreover, type-I IFN signaling on DCs was found to be essential in mice for tumor rejection by the innate and adaptive immune system. Targeted delivery of IFN-α by DCs to immune cells could boost the generation of anti-tumor immunity, while av...
Source: Cancer Immunology, Immunotherapy - April 12, 2015 Category: Cancer & Oncology Source Type: research

Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T
Abstract Chimeric antigen receptor-modified T cell (CAR-T) technology, a promising immunotherapeutic tool, has not been applied specifically to treat liver metastases (LM). While CAR-T delivery to LM can be optimized by regional intrahepatic infusion, we propose that liver CD11b+Gr-1+ myeloid-derived suppressor cells (L-MDSC) will inhibit the efficacy of CAR-T in the intrahepatic space. We studied anti-CEA CAR-T in a murine model of CEA+ LM and identified mechanisms through which L-MDSC expand and inhibit CAR-T function. We established CEA+ LM in mice and studied purified L-MDSC and responses to treatment with int...
Source: Cancer Immunology, Immunotherapy - April 8, 2015 Category: Cancer & Oncology Source Type: research

Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients
Abstract Tumor immune escape has recently been shown to be related to the development of an immune tolerance state of the microenvironment. Cytokines activating the immune system such as IFN-γ can be used to reverse the immune escape and thus to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18 stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes (TILs) in combination with intratumoral TG1042 injection (adenovirus expressing IFN-γ). The primary objective was to investigate the safety of treatment. Secondary objectives were to study the clinical re...
Source: Cancer Immunology, Immunotherapy - April 6, 2015 Category: Cancer & Oncology Source Type: research