Immunogenicity and efficacy of a rationally designed vaccine against vascular endothelial growth factor in mouse solid tumor models
AbstractVascular endothelial growth factor (VEGF) plays an important role in the progression of various cancers. The VEGF-specific antibody bevacizumab combined with chemotherapy was shown to significantly improve progression-free survival in certain cancers. However, repeated administration is necessary for effective suppression of VEGF, thereby making the therapy expensive and cumbersome. Thus, it is urgent to develop alternative reagents such as VEGF vaccines. Here we report that DTT-VEGF, a VEGF-based antigen consisting of the receptor-binding domain of VEGF and diphtheria toxin T domain (DTT), not only stimulated neut...
Source: Cancer Immunology, Immunotherapy - November 21, 2016 Category: Cancer & Oncology Source Type: research

Elevated systemic interleukin-7 in patients with colorectal cancer and individuals at high risk of cancer: association with lymph node involvement and tumor location in the right colon
AbstractInterleukin (IL)-7 is a cytokine essential for protective immunity, and it is considered as a promising agent for cancer immunotherapy. Recent studies, however, appear to associate IL-7 with aggressiveness of solid tumors. The IL-7 has been less studied in colorectal cancer (CRC) and conditions associated with increased risk of CRC development. To explore IL-7 status in bowel diseases, it was measured immunofluorometrically in 431 individuals (110 with CRC) by using Luminex platform. A level of IL-7 in CRC patients was significantly higher than in controls, did not differ from those with adenomas, but was lower tha...
Source: Cancer Immunology, Immunotherapy - November 19, 2016 Category: Cancer & Oncology Source Type: research

Elevated regulatory T cells, surface and intracellular CTLA-4 expression and interleukin-17 in the lung cancer microenvironment in humans
AbstractRegulatory T cells (Tregs) play an important role in the suppression of the immune response in lung cancer. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) expressed on T lymphocytes is capable of downregulating cytotoxic T cells and is constitutively expressed on Tregs. Little is known about the population of Tregs with two forms of CTLA-4: surface (s) and intracellular (in) in the lung cancer environment. Th17 cells defined by production of IL-17 have pleiotropic functions in anticancer immune response. Our aim was to detect the elements of immune response regulation in lung cancer in three compartments: by analysis of...
Source: Cancer Immunology, Immunotherapy - November 19, 2016 Category: Cancer & Oncology Source Type: research

Oncolysate-loaded Escherichia coli bacterial ghosts enhance the stimulatory capacity of human dendritic cells
AbstractThe natural adjuvant properties of bacterial ghosts (BGs) lie within the presence of intact pathogen-associated molecular patterns on their surface. BGs can improve the direct delivery, natural processing and presentation of target antigens within dendritic cells (DCs). Moreover, sensitization of human DCs by cancer cell lysate (oncolysate)-loaded BGs in the presence of IFN- α and GM-CSF enhanced DC maturation as indicated by an increased expression of maturation markers and co-stimulatory molecules, higher production of IL-12p70 and stimulation of significantly increased proliferation of both autologous CD4+...
Source: Cancer Immunology, Immunotherapy - November 18, 2016 Category: Cancer & Oncology Source Type: research

A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents
This study demonstrates that the 3D heterotypic spheroid model provides a novel and versatile tool for in vitro evaluation of cancer immunotherapy agents and allows for assessment of additional aspects of the activity of cancer immunotherapy agents, including a nalysis of immune cell infiltration and drug targeting. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 17, 2016 Category: Cancer & Oncology Source Type: research

Interleukin 10 expression is related to aggressiveness and poor prognosis of patients with thyroid cancer
AbstractMost patients with thyroid cancer will evolve very well with current therapies. However, 10 –30% of these patients will present recurrent disease and some of them will eventually die. IL-10 is an anti-inflammatory and immunosuppressive cytokine that can contribute to the immune escape of neoplastic cells. We aimed to investigate IL-10 as a molecular marker to improve the clinical managem ent of patients with thyroid cancer. We retrospectively studied 162 patients with follicular cell-derived thyroid cancer who attended to our institution, including 63 classic papillary thyroid carcinomas, 46 follicular varian...
Source: Cancer Immunology, Immunotherapy - November 17, 2016 Category: Cancer & Oncology Source Type: research

Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy
ConclusionAn increased number of tumour-infiltrating T cells and PD-L1 expression in metastases compared with primary tumours, suggesting accessibility for T cells, could imply that osteosarcoma patients with metastatic disease may benefit from T-cell-based immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 16, 2016 Category: Cancer & Oncology Source Type: research

Efficacy and toxicity of rechallenge with combination immune checkpoint blockade in metastatic melanoma: a case series
ConclusionsRetreatment with ipi  + nivo may be considered an option in carefully selected, well-informed patients. More research is required to delineate the benefits and risks with this approach. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 12, 2016 Category: Cancer & Oncology Source Type: research

Immunological effects of a novel RNA-based adjuvant in liver cancer patients
AbstractEvaluation of biological effects of adjuvants on immune cells has been assessed in a limited number of studies. Moreover, no data are available on samples derived from cancer patients who may have a severe immune impairment. The effects of a novel RNA-based adjuvant (RNAdjuvant® developed by CureVac) were assessed in an ex vivo setting on PBMCs obtained from 8 healthy volunteers and 17 HCC patients, using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression, cytokine production as well as gene expression was performed. Moreover, the dow...
Source: Cancer Immunology, Immunotherapy - November 10, 2016 Category: Cancer & Oncology Source Type: research

Phase I –II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints
AbstractThis phase I –II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1–16) and alemtuzumab (weeks 5–16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1–29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose wa...
Source: Cancer Immunology, Immunotherapy - November 4, 2016 Category: Cancer & Oncology Source Type: research

Neutrophils from chronic lymphocytic leukemia patients exhibit an increased capacity to release extracellular traps (NETs)
AbstractChronic lymphocytic leukemia (CLL) is characterized by immune defects that contribute to a high rate of infections and autoimmune cytopenias. Neutrophils are the first line of innate immunity and respond to pathogens through multiple mechanisms, including the release of neutrophil extracellular traps (NETs). These web-like structures composed of DNA, histones, and granular proteins are also produced under sterile conditions and play important roles in thrombosis and autoimmune disorders. Here we show that neutrophils from CLL patients are more prone to release NETs compared to those from age-matched healthy donors ...
Source: Cancer Immunology, Immunotherapy - October 28, 2016 Category: Cancer & Oncology Source Type: research

Alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 can support immune responses toward tumors overexpressing ganglioside D3 in mice
AbstractAn immunotherapeutic strategy is discussed supporting anti-tumor activity toward malignancies overexpressing ganglioside D3. GD3 can be targeted by NKT cells when derived moieties are presented in the context of CD1d. NKT cells can support anti-tumor responses by secreting inflammatory cytokines and through cytotoxicity toward CD1d+GD3+ tumors. To overexpress GD3, we generated expression vector DNA and an adenoviral vector encoding the enzyme responsible for generating GD3 from its ubiquitous precursor GM3. We show that DNA encoding α-N-acetyl-neuraminide α-2,8-sialyltransferase 1 (SIAT8) introduced by ...
Source: Cancer Immunology, Immunotherapy - October 27, 2016 Category: Cancer & Oncology Source Type: research

High-efficiency lysis of cervical cancer by allogeneic NK cells derived from umbilical cord progenitors is independent of HLA status
AbstractDown-regulation of HLA in tumor cells, low numbers and dysfunctionality of NK cells are commonly observed in patients with end-stage cervical cancer. Adoptive transfer of high numbers of cytotoxic NK cells might be a promising treatment approach in this setting. Here, we explored the cytotoxic efficacy on ten cervical cancer cell lines of activated allogeneic NK cells from two sources, i.e., peripheral blood (PBNK) with and without cetuximab (CET), a tumor-specific monoclonal antibody directed against EGFR, or derived from umbilical cord blood (UCB-NK). Whereas CET monotherapy was ineffective against the panel of c...
Source: Cancer Immunology, Immunotherapy - October 25, 2016 Category: Cancer & Oncology Source Type: research

Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report
ConclusionsImmune checkpoint inhibitors should be avoided in allograft recipients but high-intensity immunosuppression is effective to salvage allograft rejection induced by these agents. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 22, 2016 Category: Cancer & Oncology Source Type: research

Heterogeneity of CD8 + tumor-infiltrating lymphocytes in non-small-cell lung cancer: impact on  patient prognostic assessments and comparison of quantification by different sampling strategies
ConclusionDifferent tumor sampling strategies may yield discordant TIL density results and different stratification for risk assessment. Small biopsies may be particularly unrepresentative. Random sampling of larger tumor areas is recommended. Enumerating CD8+ T cells in the tumor center may have prognostic value. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 21, 2016 Category: Cancer & Oncology Source Type: research

A case of pembrolizumab-induced type-1 diabetes mellitus and discussion of immune checkpoint inhibitor-induced type 1 diabetes
AbstractImmune checkpoint inhibitors such as pembrolizumab, ipilimumab, and nivolumab, now FDA-approved for use in treating several types of cancer, have been associated with immune-related adverse effects. Specifically, the antibodies targeting the programmed-cell death-1 immune checkpoint, pembrolizumab and nivolumab, have been rarely reported to induce the development of type 1 diabetes mellitus. Here we describe a case of a patient who developed antibody-positive type 1 diabetes mellitus following treatment with pembrolizumab in combination with systemic chemotherapy for metastatic adenocarcinoma of the lung. We will a...
Source: Cancer Immunology, Immunotherapy - October 19, 2016 Category: Cancer & Oncology Source Type: research

Effective induction of cytotoxic T cells recognizing an epitope peptide derived from hypoxia-inducible protein 2 (HIG2) in patients with metastatic renal cell carcinoma
ConclusionsHIG2-9-4 peptide vaccine treatment was tolerable and effectively induced peptide-specific CTLs in RCC patients. This novel peptide vaccine therapy for RCC is promising. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 18, 2016 Category: Cancer & Oncology Source Type: research

5T4 oncofoetal antigen: an attractive target for immune intervention in cancer
AbstractThe natural history of a patient ’s cancer is often characterised by genetic diversity and sequential sweeps of clonal dominance. It is therefore not surprising that identifying the most appropriate tumour-associated antigen for targeted intervention is challenging. The 5T4 oncofoetal antigen was identified by searching for surfa ce molecules shared between human trophoblast and cancer cells with the rationale that they may function to allow survival of the foetus as a semi-allograft in the mother or a tumour in its host. The 5T4 protein is expressed by many different cancers but rarely in normal adult tissue...
Source: Cancer Immunology, Immunotherapy - October 18, 2016 Category: Cancer & Oncology Source Type: research

Low-dose interleukin-2 impairs host anti-tumor immunity and inhibits therapeutic responses in a mouse model of melanoma
AbstractRecombinant interleukin-2 (rIL-2) is associated with objective responses in 15 –20 % of patients with metastatic melanoma and renal cell carcinoma. More recently, rIL-2 has also demonstrated improved clinical activity in patients with melanoma. Given the toxicity of high-dose rIL-2 and the availability of many new immunotherapy agents, it has been suggested that lower doses of rIL-2 may be preferred for combination clinical studies. In order to determine the impact of low doses of rIL-2 on anti-tumor immunity and therapeutic effectiveness, we challenged C57BL/6 mice with poorly immunogenic B16-F10 melano...
Source: Cancer Immunology, Immunotherapy - October 18, 2016 Category: Cancer & Oncology Source Type: research

Rationale and evidence to combine radiation therapy and immunotherapy for cancer treatment
AbstractCancer immunotherapy exploits the immune system ’s ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinic al use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT). An incre...
Source: Cancer Immunology, Immunotherapy - October 14, 2016 Category: Cancer & Oncology Source Type: research

Anti-GITR therapy promotes immunity against malignant glioma in a murine model
In this study, we examined the modality of the antibody function at the tumor site as opposed to the periphery as the blood –brain barrier prevents efficient antibody delivery to brain tumors. Mice harboring established GL261 tumors were treated with anti-GITR monotherapy and were shown to have a significant increase in overall survival (p 
Source: Cancer Immunology, Immunotherapy - October 12, 2016 Category: Cancer & Oncology Source Type: research

Surface biotinylation of cytotoxic T lymphocytes for in vivo tracking of tumor immunotherapy in murine models
AbstractCurrently, there is no stable and flexible method to label and track cytotoxic T lymphocytes (CTLs) in vivo in CTL immunotherapy. We aimed to evaluate whether the sulfo-hydroxysuccinimide (NHS)-biotin –streptavidin (SA) platform could chemically modify the cell surface of CTLs for in vivo tracking. CD8+ T lymphocytes were labeled with sulfo-NHS-biotin under different conditions and then incubated with SA–Alexa647. Labeling efficiency was proportional to sulfo-NHS-biotin concentration. CD8+ T lymphocytes could be labeled with higher efficiency with sulfo-NHS-biotin in DPBS than in RPMI (P 
Source: Cancer Immunology, Immunotherapy - October 8, 2016 Category: Cancer & Oncology Source Type: research

Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma
AbstractHigh-dose interleukin-2 (HD IL-2) was approved for treatment of metastatic renal cell carcinoma (mRCC) in 1992 and for metastatic melanoma (mM) in 1998, in an era predating targeted therapies and immune checkpoint inhibitors. The PROCLAIMSM registry was established to collect and analyze data for patients treated with HD IL-2 in the current era. This analysis includes 170 patients with mM and 192 patients with mRCC treated between 2005 and 2012 with survival data current as of July 27, 2015. For patients with mM, complete response (CR) was observed in 5  %, partial response (PR) in 10 %, stable disease (S...
Source: Cancer Immunology, Immunotherapy - October 6, 2016 Category: Cancer & Oncology Source Type: research

Tumor-directed immunotherapy can generate tumor-specific T cell responses through localized co-stimulation
AbstractThe most important goals for the field of immuno-oncology are to improve the response rate and increase the number of tumor indications that respond to immunotherapy, without increasing adverse side effects. One approach to achieve these goals is to use tumor-directed immunotherapy, i.e., to focus the immune activation to the most relevant part of the immune system. This may improve anti-tumor efficacy as well as reduce immune-related adverse events. Tumor-directed immune activation can be achieved by local injections of immune modulators in the tumor area or by directing the immune modulator to the tumor using bis...
Source: Cancer Immunology, Immunotherapy - October 6, 2016 Category: Cancer & Oncology Source Type: research

Erratum to: NK cell-mediated antibody-dependent cellular cytotoxicity is enhanced by tamoxifen in HER2/neu non-amplified, but not HER2/neu-amplified, breast cancer cells
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 1, 2016 Category: Cancer & Oncology Source Type: research

Killer immunoglobulin-like receptor (KIR) and KIR –ligand genotype do not correlate with clinical outcome of renal cell carcinoma patients receiving high-dose IL2
AbstractNK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR –ligand interactions. Inhibitory KIR–ligands have been identified as HLA molecules, while activating KIR–ligands are largely unknown. Individuals that have not inherited the corresponding KIR–ligand for at least one inhibitory KIR gene are termed the “KIR–ligand missing” genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR–ligand is missing on autologous tissu...
Source: Cancer Immunology, Immunotherapy - September 30, 2016 Category: Cancer & Oncology Source Type: research

Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy with fusions of dendritic and glioma cells in patients with glioblastoma
ConclusionsThe combination of TMZ-treatment leading to up-regulation and/or cytoplasmic accumulation of CAPs, with FC-immunotherapy as a means of producing specific immunity against CAPs, may safely induce anti-tumor effects in patients with GBM. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 29, 2016 Category: Cancer & Oncology Source Type: research

Predicting PD-L1 expression on human cancer cells using next-generation sequencing information in computational simulation models
ConclusionThis concept can easily be extended to cancer patient cells where an accurate method to predict PD-L1 expression would affirm IHC results and improve its potential as a biomarker and a clinical predictor of treatment success. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 29, 2016 Category: Cancer & Oncology Source Type: research

Anti-PD-1 inhibits Foxp3 + Treg cell conversion and unleashes intratumoural effector T cells thereby enhancing the efficacy of a cancer vaccine in a mouse model
AbstractThe co-inhibitory molecule PD-1 suppresses T cell responses and has been targeted in the treatment of cancer. Here, we examined the role of PD-1 in regulating the balance between regulatory and effector T cells and whether blocking PD-1 could enhance tumour vaccine-induced protective immunity. A significantly higher proportion of tumour-resident T cells expressed PD-1 and Foxp3 compared with T cells in the tumour circulation or draining lymph nodes, and this correlated with a lower frequency of IFN- γ- and TNF-secreting CD8 T cells. Blocking PD-1 with a specific antibody reduced Foxp3+ regulatory T (Treg) cel...
Source: Cancer Immunology, Immunotherapy - September 28, 2016 Category: Cancer & Oncology Source Type: research

Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells
In this study, we investigated the interaction between PD-1 on iNKT cells and PDL on antigen-presenting cells (APCs) in the context of iNKT cell stimulation. The blockade of PDL1 at the time of stimulation resulted in increased release of helper T cell (Th) 1 cytokines from iNKT cells, leading to the activation of NK cells. The direct antitumor function of iNKT cells was also enhanced after stimulation with anti-PDL1 antibody-treated APCs. According to these results, we conclude that the co-administration of anti-PDL1 antibody and alpha-galactosylceramide ( αGalCer)-pulsed APCs enhances iNKT cell-mediated antitumor i...
Source: Cancer Immunology, Immunotherapy - September 15, 2016 Category: Cancer & Oncology Source Type: research

Macrophage migration inhibitory factor (MIF) is induced by cytotoxic drugs and is involved in immune escape and migration in childhood rhabdomyosarcoma
AbstractMacrophage migration inhibitory factor (MIF) is known to be involved in oncogenic transformation, tumour progression, and immunosuppression and is overexpressed in many solid tumours, including paediatric rhabdomyosarcoma (RMS). We investigated the function of MIF in RMS during treatment with cytotoxic drugs. RMS cell lines were analysed by flow cytometry, immunofluorescence staining, and ELISA. We demonstrated the overexpression of MIF in RMS cells and the enhanced expression and secretion after treatment with cytotoxic agents. Migration assays of RMS cells revealed that inhibitors of MIF (ISO-1, Ant.III 4-IPP, An...
Source: Cancer Immunology, Immunotherapy - September 15, 2016 Category: Cancer & Oncology Source Type: research

Potential use of lymph node-derived HPV-specific T cells for adoptive cell therapy of cervical cancer
In conclusion, TDLN represent a rich source of polyclonal HPV16 E6- and E7-specific T cells, which can be expanded under clinical grade conditions for adoptive immunotherapy in patients wi th cervical cancer. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 12, 2016 Category: Cancer & Oncology Source Type: research

“Cancer Bio-Immunotherapy in Siena”: Thirteenth Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT), Siena, Italy, October 8–10, 2015
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 12, 2016 Category: Cancer & Oncology Source Type: research

Histone deacetylase inhibitors enhance CD1d-dependent NKT cell responses to lymphoma
In this study, we pre-treated CD1d-expressing tumor cells with HDAC inhibitors (HDACi) and assessed CD1d-dependent NKT cell responses to mantle cell lymphoma (MCL). Pre-treatment with Trichostatin-A, a pan-HDACi, rapidly enhanced both CD1d- and MHC class II-mediated antigen presentation. Similarly, treatment of MCL cells with other HDACi resulted in enhanced CD1d-dependent NKT cell responses. The observed changes are due, at least in part, to an increase in bothCD1D mRNA and CD1d cell surface expression. Mechanistically, we found that HDAC2 binds to theCD1D promoter. Knockdown of HDAC2 in tumor cells resulted in a signific...
Source: Cancer Immunology, Immunotherapy - September 10, 2016 Category: Cancer & Oncology Source Type: research

Regulatory T cells function at the early stage of tumor progression in a mouse model of tongue squamous cell carcinoma
The objective of this study was to observe the distribution of regulatory T cells (Tregs) in the development of tongue squamous cell carcinoma (SCC) and to determine the role of Tregs in the progression of tongue SCC. A mouse model of 4-nitroquinoline-1-oxide (4NQO)-induced-tongue SCC was established. The expression of Forkhead box P3 (Foxp3), interleukin 10, transforming growth factor- β, chemokine CC motif ligands 17, 20, and CC chemokine receptor 4 was determined using real-time quantitative polymerase chain reaction. Foxp3 expression was also analyzed using immunohistochemistry. The results were compared with thos...
Source: Cancer Immunology, Immunotherapy - September 10, 2016 Category: Cancer & Oncology Source Type: research

The growing world of CAR T cell trials: a systematic review
AbstractIn recent years, cancer treatment involving adoptive cell therapy with chimeric antigen receptor (CAR)-modified patient ’s immune cells has attracted growing interest. Using gene transfer techniques, the patient’s T cells are modified ex vivo with a CAR which redirects the T cells toward the cancer cells through an antibody-derived binding domain. The T cells are activated by the CAR primary signaling and costimu latory domains. Such “second generation” CAR T cells induced complete remission of B cell malignancies in the long-term. In this fast-moving field with a growing number of engineere...
Source: Cancer Immunology, Immunotherapy - September 9, 2016 Category: Cancer & Oncology Source Type: research

Complete response to nivolumab monotherapy in a treatment-naive, BRAF wild-type patient with advanced mucosal melanoma and elevated lactate dehydrogenase: a case report from a phase III trial
AbstractThe anti-PD-1 agent, nivolumab, has been approved both as monotherapy and in combination with ipilimumab for the treatment of unresectable or metastatic melanoma in the USA and European Union. Here we present the case of a patient with treatment-naive, metastatic mucosal melanoma and baseline LDH approximately seven times the upper limit of normal. The patient was enrolled in a clinical trial (CheckMate 066) and achieved a partial response, followed by a durable complete response with nivolumab treatment. The patient ’s LDH levels were documented in each cycle and dropped markedly within 2 months, when p...
Source: Cancer Immunology, Immunotherapy - September 7, 2016 Category: Cancer & Oncology Source Type: research

Mass spectrometric analysis of the HLA class I peptidome of melanoma cell lines as a promising tool for the identification of putative tumor-associated HLA epitopes
AbstractMelanoma is one of the most immunogenic tumors, and extensive lists of potential tumor rejection antigens have been collected during the last decades. By isolating human leukocyte antigen (HLA) class I complexes from five melanoma cell lines (FM-82, FM-93/2, Mel-624, MeWo and SK-Mel-5) and sequencing HLA-eluted peptides by mass spectrometry, we identified over 10,000 unique peptides with high confidence. The majority of the peptides were 8 –11 amino acids in length and were predicted to bind to the respective HLA alleles. Over 250 epitopes, corresponding to previously described tumor-associated antigens, were...
Source: Cancer Immunology, Immunotherapy - September 6, 2016 Category: Cancer & Oncology Source Type: research

The role of Ly49E receptor expression on murine intraepithelial lymphocytes in intestinal cancer development and progression
AbstractLy49E is a member of the Ly49 family of NK receptors and is distinct from other members of this family on the basis of its structural properties, expression pattern and ligand recognition. Importantly, Ly49E receptor expression is high on small intestinal and colonic intraepithelial lymphocytes (IELs). Intestinal IELs are regulators of the mucosal immune system and contribute to front-line defense at the mucosal barrier, including anti-tumor immune response. Whereas most Ly49 receptors have MHC class-I ligands, we showed that Ly49E is instead triggered by urokinase plasminogen activator (uPA). uPA has been extensiv...
Source: Cancer Immunology, Immunotherapy - September 1, 2016 Category: Cancer & Oncology Source Type: research

Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies
AbstractTumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune r...
Source: Cancer Immunology, Immunotherapy - September 1, 2016 Category: Cancer & Oncology Source Type: research

A phase I study of recombinant (r) vaccinia-CEA(6D)-TRICOM and rFowlpox-CEA(6D)-TRICOM vaccines with GM-CSF and IFN- α-2b in patients with CEA-expressing carcinomas
AbstractPrime-boost vaccination with recombinant (r) vaccinia(V)-CEA(6D)-TRICOM (triad of co-stimulatory molecules B7.1, ICAM-1 and LFA-3) and rFowlpox(F)-CEA(6D)-TRICOM infect antigen-presenting cells and direct expression of co-stimulatory molecules. We hypothesized that co-administration of vaccine with GM-CSF and interferon alpha (IFN- α) would have efficacy in CEA-expressing cancers. Patients with CEA-expressing cancers received the rV-CEA(6D)-TRICOM vaccine subcutaneously (s.c.) on day 1 followed by GM-CSF s.c. to the injection site on days 1–4. In Cycle 1, patients received thrice weekly s.c. injections ...
Source: Cancer Immunology, Immunotherapy - August 31, 2016 Category: Cancer & Oncology Source Type: research

Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma
AbstractSurvivin is an anti-apoptotic protein that is highly expressed in many cancers, including malignant gliomas. Preclinical studies established that the conjugated survivin peptide mimic SurVaxM (SVN53-67/M57-KLH) could stimulate an anti-tumor immune response against murine glioma in vivo, as well as human glioma cells ex vivo. The current clinical study was conducted to test safety, immunogenicity and clinical effects of the vaccine. Recurrent malignant glioma patients whose tumors were survivin-positive, and who had either HLA-A*02 or HLA-A*03 MHC class I allele-positivity, were given subcutaneous injections of SurV...
Source: Cancer Immunology, Immunotherapy - August 30, 2016 Category: Cancer & Oncology Source Type: research

NK cell-mediated antibody-dependent cellular cytotoxicity is enhanced by tamoxifen in HER2/neu non-amplified, but not HER2/neu-amplified, breast cancer cells
In this study, tamoxifen was used to increase HER2/neu protein level to determine whether increased tumor antigen expression could enhance NK cell-mediated antibody-dependent cytotoxicity (ADCC). Tamoxifen was found to increase HER2/neu 1.5-fold to threefold in breast cancer cell lines that were HER2/neu non-amplified. Using flow cytometry to simultaneously evaluate NK cell degranulation and tumor cell death, the increase in HER2/neu enhanced NK cell-mediated ADCC. However, in cells that had HER2/neu gene amplification and estrogen receptor expression, tamoxifen elevated HER2/neu but failed to improve NK cell function. The...
Source: Cancer Immunology, Immunotherapy - August 29, 2016 Category: Cancer & Oncology Source Type: research

Quantification of PD-L1 and PD-1 expression on tumor and immune cells in non-small cell lung cancer (NSCLC) using non-enzymatic tissue dissociation and flow cytometry
We report a truly quantitative technology for PD-L1 expression in non-small cell lung cancer (NSCLC). In addition, we present a non-enzymatic technology that creates a cell suspension from fresh tumor tissue so that either fine-needle aspiration (FNA) or fresh tissue can be used in this assay.MethodsNon-enzymatic tissue homogenization (IncellPREP; IncellDx, Menlo Park, California) was performed on 4-mm punch biopsies. An FNA was taken from the same tumor to create matched sample sets. Cells were labeled with antibodies directed against CD45, PD-1, and PD-L1 and then stained with DAPI to identify intact, single cells, and t...
Source: Cancer Immunology, Immunotherapy - August 26, 2016 Category: Cancer & Oncology Source Type: research

The fifteenth International Conference on Progress in Vaccination against Cancer (PIVAC-15), 6 –8 October 2015, Tübingen, Germany: looking back on 15 years of progress
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 24, 2016 Category: Cancer & Oncology Source Type: research

A panel of autoantibodies against multiple tumor-associated antigens in the immunodiagnosis of esophageal squamous cell cancer
AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China with very low 5-year survival rate mostly due to the paucity of effective early diagnostic methods. Serum autoantibodies against 9 tumor-associated antigens (TAAs) from ESCC patients and healthy controls were detected by enzyme-linked immunosorbent assay to evaluate their performances in the immunodiagnosis of ESCC. Logistic regression models were generated to predict the probability of individuals being diagnosed with ESCC in training cohort (648 participants) and further validated in another independent cohort (372 participants)....
Source: Cancer Immunology, Immunotherapy - August 23, 2016 Category: Cancer & Oncology Source Type: research

Immunological evaluation of personalized peptide vaccination for patients with histologically unfavorable carcinoma of unknown primary site
AbstractThe immunological characteristics of carcinoma of unknown primary site (CUP) are not well established due to inclusion of heterogeneous types of metastatic tumors with the absence of any detectable primary site. We evaluated the immune responses in patients with histologically unfavorable CUP during personalized peptide vaccination (PPV). Ten patients with histologically unfavorable CUP who had been treated by PPV after chemotherapy failure were analyzed. In PPV treatment, up to four human leukocyte antigen-matched peptides of a total 31 peptides were selected according to preexisting host immunity before vaccinati...
Source: Cancer Immunology, Immunotherapy - August 22, 2016 Category: Cancer & Oncology Source Type: research

Immunosenescence: limitations of natural killer cell-based cancer immunotherapy
AbstractCancer is primarily considered a disease of old age. Immunosenescence refers to the age-associated changes in the immune system, and its contribution to the increased risk of cancer in old individuals has been discussed for many years. Natural killer (NK) cells are cytotoxic innate immune cells specialized in defence against tumour and virus-infected cells. NK cell cytotoxicity is the result of a fine balance between activating and inhibitory receptors. Several activating receptors have been identified that recognize different ligands frequently found over-expressed on tumour cells or virus-infected cells. The most...
Source: Cancer Immunology, Immunotherapy - August 16, 2016 Category: Cancer & Oncology Source Type: research

Prognostic significance of HLA class I and II expression in patients with diffuse large B cell lymphoma treated with standard chemoimmunotherapy
AbstractLoss of tumor cell human leukocyte antigen (HLA) is an immune escape mechanism for malignancies. However, the effect of low HLA class I or class II expression in diffuse large B cell lymphoma (DLBCL) treated with chemoimmunotherapy with the monoclonal antibody rituximab is largely unknown. We retrospectively analyzed samples and other data from 144 patients with DLBCL who were newly diagnosed in our institution and treated with standard R-CHOP therapy. We used antibodies against pan-HLA class I and pan-HLA class II molecules to assess HLA expression and its effect on prognosis. In a multivariate analysis, loss of H...
Source: Cancer Immunology, Immunotherapy - August 13, 2016 Category: Cancer & Oncology Source Type: research

Intratumoral interferon-gamma increases chemokine production but fails to increase T cell infiltration of human melanoma metastases
ConclusionThe melanoma vaccine induced circulating T cell responses, but it failed to infiltrate metastases, thus highlighting the need for combination strategies to support T cell infiltration. A single intratumoral injection of IFN γ induced T cell-attracting chemokines; however, it also induced secondary immune regulation that may paradoxically limit immune infiltration and effector functions. Alternate dosing strategies or additional combinatorial treatments may be needed to promote trafficking and retention of tumor-reacti ve T cells in melanoma metastases. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 13, 2016 Category: Cancer & Oncology Source Type: research