Immunotherapy with cancer peptides in combination with intravesical bacillus Calmette –Guerin for patients with non-muscle invasive bladder cancer
ConclusionsCancer peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 3, 2018 Category: Cancer & Oncology Source Type: research

mTOR-mediated glycolysis contributes to the enhanced suppressive function of murine tumor-infiltrating monocytic myeloid-derived suppressor cells
In this study, we found that tumor-infiltrating M-MDSCs had the same phenotype with splenic M-MDSCs. Compared with splenic M-MDSCs, tumor-infiltrating M-MDSCs exhibited stronger suppressive activities which was accompanied by higher glycolysis. Inhibition of glycolysis impaired the suppressive function of tumor M-MDSCs. Meanwhile, the results demonstrated that mTOR was responsible for this function regulation. mTOR inhibition by rapamycin decreased the glycolysis and reduced the suppressive activities of these cells. Furthermore, rapamycin treatment inhibited the tumor growth and reduced the percentage of M-MDSCs in 3LL tu...
Source: Cancer Immunology, Immunotherapy - July 2, 2018 Category: Cancer & Oncology Source Type: research

Peripheral monocytes and neutrophils predict response to immune checkpoint inhibitors in patients with metastatic non-small cell lung cancer
AbstractWe carried out a retrospective cohort study on patients with metastatic non-small cell lung cancer (mNSCLC) to identify the peripheral blood count parameters associated with response to immune checkpoint inhibitors (ICIs). There were 17 males and 15 females. Their median age was 64.5  years (range 20–84). History of smoking was present in 25/32 (78%) patients. Twelve patients received pembrolizumab, 19 patients nivolumab, and one patient nivolumab followed by pembrolizumab. Responses were observed in 19/32 (59%) patients, all partial responses. There was no difference in the distribution of sex, age, and...
Source: Cancer Immunology, Immunotherapy - July 2, 2018 Category: Cancer & Oncology Source Type: research

Indoleamine 2,3-dioxygenase provides adaptive resistance to immune checkpoint inhibitors in hepatocellular carcinoma
AbstractHepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Immune checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies has shown promising results in the treatment of patients with advanced HCC. The anti-PD-1 antibody, nivolumab, is now approved for patients who have had progressive disease on the current standard of care. However, a subset of patients with advanced HCC treated with immune checkpoint inhibitors failed to respond to therapy. Here, we provide evidence of adaptive resistance to immune checkpoint inhibitors through upregulation of indoleamine 2,3-dioxygenase ...
Source: Cancer Immunology, Immunotherapy - June 29, 2018 Category: Cancer & Oncology Source Type: research

Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological challenge
AbstractTreatment of malignant pleural mesothelioma (MPM) represents a highly unmet medical need. Here, we discuss the results and therapeutic potential of first- and second-generation immunomodulatory antibodies targeting distinct immune checkpoints for the treatment of MPM, as well as their prospective therapeutic role in combination strategies. We also discuss the role of appropriate radiological criteria of response for MPM and the potential need ofad hoc criteria of disease evaluation in MPM patients undergoing treatment with immunotherapeutic agents. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 26, 2018 Category: Cancer & Oncology Source Type: research

Dendritic cell trafficking in tumor-bearing mice
AbstractProstate cancer is one of the leading causes of cancer deaths, with no curative treatments once it spreads. Alternative therapies, including immunotherapy, have shown limited efficacy. Dendritic cells (DC) have been widely used in the treatment of various malignancies. DC capture antigens and move to the lymphoid organs where they prime naive T cells. Interaction between DC and T cells are most active in lymph nodes and suppression of DC trafficking to lymph nodes impairs the immune response. In this work, we aimed to study trafficking of DC in vivo via various routes of delivery, to optimize the effectiveness of D...
Source: Cancer Immunology, Immunotherapy - June 25, 2018 Category: Cancer & Oncology Source Type: research

Expression of CD3, PD-L1 and CTLA-4 in mammary and extra-mammary Paget disease
ConclusionPaget disease is characterized by an intense lymphocytic response, devoid of the immune-suppressive impact of the PD-L1 pathway, but with occasional CTLA-4 expression. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 25, 2018 Category: Cancer & Oncology Source Type: research

Antibody-dependent cell-mediated cytotoxicity induced by active immunotherapy based on racotumomab in non-small cell lung cancer patients
AbstractAntitumor strategies based on positive modulation of the immune system currently represent therapeutic options with prominent acceptance for cancer patients ’ treatment due to its selectivity and higher tolerance compared to chemotherapy. Racotumomab is an anti-idiotype (anti-Id) monoclonal antibody (mAb) directed to NeuGc-containing gangliosides such as NeuGcGM3, a widely reported tumor-specific neoantigen in many human cancers. Racotumomab has been approved in Latin American countries as an active immunotherapy for advanced non-small cell lung cancer (NSCLC) treatment. In this work, we evaluated the inducti...
Source: Cancer Immunology, Immunotherapy - June 23, 2018 Category: Cancer & Oncology Source Type: research

Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models
AbstractAdenosine signaling via the A2a receptor (A2aR) is emerging as an important checkpoint of immune responses. The presence of adenosine in the inflammatory milieu or generated by the CD39/CD73 axis on tissues or T regulatory cells serves to regulate immune responses. By nature of the specialized metabolism of cancer cells, adenosine levels are increased in the tumor microenvironment and contribute to tumor immune evasion. To this end, small molecule inhibitors of the A2aR are being pursued clinically to enhance immunotherapy. Herein, we demonstrate the ability of the novel A2aR antagonist, CPI-444, to dramatically en...
Source: Cancer Immunology, Immunotherapy - June 19, 2018 Category: Cancer & Oncology Source Type: research

Fighting breast cancer stem cells through the immune-targeting of the xCT cystine –glutamate antiporter
In conclusion, our approach based on the comparison of the transcriptome of tumorspheres and parental cells allowed us to identify a novel CSC-related target and to develop preclinical therapeutic approaches able to impac t on CSC biology, and therefore, hampering tumor growth and dissemination. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 15, 2018 Category: Cancer & Oncology Source Type: research

Blood cell count indexes as predictors of outcomes in advanced non-small-cell lung cancer patients treated with Nivolumab
AbstractLung cancer is the most common malignancy worldwide. Despite significant advances in diagnosis and treatment, mortality rates remain extremely high, close to incidence rates. Several targeted therapies have been recently introduced for the treatment of non-small cell lung cancer (NSCLC), the most common type of lung cancer. Nivolumab, a monoclonal antibody that targets programmed death-1 (PD-1), was the first immune checkpoint inhibitor approved for the treatment of patients with advanced/metastatic NSCLC not responding to platinum-based chemotherapy. Biomarkers predicting response to these therapies would allow ea...
Source: Cancer Immunology, Immunotherapy - June 9, 2018 Category: Cancer & Oncology Source Type: research

Longitudinal studies of the 18 F-FDG kinetics after ipilimumab treatment in metastatic melanoma patients based on dynamic FDG PET/CT
ConclusionQuantitative analysis of18F-FDG PET data does not provide additional information in treatment response evaluation of metastatic melanoma patients receiving ipilimumab. PERCIMT criteria correlated better with clinical response. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 5, 2018 Category: Cancer & Oncology Source Type: research

Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies
AbstractThe recruitment of T-cells by bispecific antibodies secreted from adoptively transferred, gene-modified autologous cells has shown satisfactory results in preclinical cancer models. Even so, the approach ’s translation into the clinic will require incremental improvements to its efficacy and reduction of its toxicity. Here, we characterized a tandem T-cell recruiting bispecific antibody intended to benefit gene-based immunotherapy approaches, which we call the light T-cell engager (LiTE), consisti ng of an EGFR-specific single-domain VHH antibody fused to a CD3-specific scFv. We generated two LiTEs with the a...
Source: Cancer Immunology, Immunotherapy - June 4, 2018 Category: Cancer & Oncology Source Type: research

Differential regulation of human monocytes and NK cells by antibody-opsonized tumors
AbstractThe monocyte network is important for therapeutic efficacy of antibody therapies against cancer. One mechanism which monocytes/macrophages use to kill cancer cells is phagocytosis. Using trastuzumab and human breast cancer cell lines as a model, we used flow cytometry to evaluate the importance of avidity, antigen density, Fc γ receptor (FcγR) expression, and FcγR polymorphisms in human monocyte phagocytosis. By increasing avidity for the tumor through the addition of pertuzumab to trastuzumab, there was a two-to-threefold increase in phagocytosis potency against the HCC1419 cell line compared to ...
Source: Cancer Immunology, Immunotherapy - May 31, 2018 Category: Cancer & Oncology Source Type: research

Targeting myeloid-derived suppressor cells for cancer immunotherapy
AbstractMyeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with an immune suppressive phenotype. They represent a critical component of the immune suppressive niche described in cancer, where they support immune escape and tumor progression through direct effects on both the innate and adaptive immune responses, largely by contributing to maintenance of a high oxidative stress environment. The number of MDSCs positively correlates with protumoral activity, and often diminishes the effectiveness of immunotherapies, which is particularly problematic with the emergence of persona...
Source: Cancer Immunology, Immunotherapy - May 31, 2018 Category: Cancer & Oncology Source Type: research

Randomized controlled phase III trial of adjuvant chemoimmunotherapy with activated cytotoxic T cells and dendritic cells from regional lymph nodes of patients with lung cancer
AbstractRandomized controlled trial of adjuvant chemoimmunotherapy for lung cancer indicated a significant advantage in patients receiving immunotherapy. Herein we report the final results and immunological analysis with a median follow-up of 59.6  months. Patients with post-surgical lung cancer were randomly designated to receive either chemoimmunotherapy (group A, immunotherapy arm) or chemotherapy (group B, control arm). The immunotherapy comprised the adoptive transfer of autologous activated killer T cells and dendritic cells (AKT–DC) . The 2- and 5-year overall survival (OS) rates were 96.0 and 69.4% in gr...
Source: Cancer Immunology, Immunotherapy - May 31, 2018 Category: Cancer & Oncology Source Type: research

Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for non-small cell lung cancer patients
AbstractAdoptive cell therapy (ACT) of tumor infiltration lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Due to the fact that metastatic lung cancer has proven to be susceptible to immunotherapy and possesses a high mutation burden, which makes it responsive to T cell attack, we explored the feasibility of TIL ACT in non-small cell lung cancer (NSCLC) patients. Multiple TIL cultures were isolated from tumor specimens of five NSCLC patients undergoing thoracic surgery. We were able to successfully establish TIL cultures by various methods from all patient...
Source: Cancer Immunology, Immunotherapy - May 29, 2018 Category: Cancer & Oncology Source Type: research

Merkel cell carcinoma and cellular cytotoxicity: sensitivity to cellular lysis and screening for potential target antigens suitable for antibody-dependent cellular cytotoxicity
This study was carried out to characterize MCC line sensitivity to cellular lysis and to identify cell surface antigens that could be used for direct targeting of this tumor. For five representative MCC lines, the absence or low expression of MICA, MICB, HLA-I, and ICAM-1 was associated with low level of recognition by NK cells and T lymphocytes. However, expression of HLA-I and ICAM-1 and sensitivity to cellular lysis could be restored or increased after exposure to INF γ. We tested 41 antibodies specific for 41 different antigens using a novel antibody-dependent cellular cytotoxicity (ADCC) screening system for tar...
Source: Cancer Immunology, Immunotherapy - May 28, 2018 Category: Cancer & Oncology Source Type: research

Occurrence of type 1 and type 2 diabetes in patients treated with immunotherapy (anti-PD-1 and/or anti-CTLA-4) for metastatic melanoma: a retrospective study
In conclusion, in addition to inducing this rare immune-related diabetes condition, anti-PD-1 treatment appears to increase CRP levels, a potential inflammatory trigger of insulin resistance, but without any short-term impact on blood glucose level. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 28, 2018 Category: Cancer & Oncology Source Type: research

Regulatory NK1.1 − CD4 + NKG2D + subset induced by NKG2DL + cells promotes tumor evasion in mice
In conclusion, we describe a regulatory NK1.1−CD4+NKG2D+ T-cell population, different from other regulatory T cells and abnormally elevated in pCD86-Rae-1 ε transgenic and MC38 tumor-bearing mice. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 25, 2018 Category: Cancer & Oncology Source Type: research

T-lymphocyte profiles differ between keratoacanthomas and invasive squamous cell carcinomas of the human skin
ConclusionsTumor-associated T-lymphocyte infiltrates showed significant differences between AK, KA and invasive cSCC. PD-L1 expression correlated with invasion of T-cell infiltrates in invasive cSCC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 24, 2018 Category: Cancer & Oncology Source Type: research

Novel non-invasive early detection of lung cancer using liquid immunobiopsy metabolic activity profiles
In this study, we present an innovative, non-invasive, cancer detection approach based on measurements of the metabolic activity profiles of immune system cells. For each Liquid ImmunoBiopsy test, a 384 multi-well plate is loaded with freshly separated PBMCs, and each well contains 1 of the 16 selected stimulants in several increasing concentrations. The extracellular acidity is measured in both air-open and hermetically-sealed states, using a commercial fluorescence plate reader, for approximately 1.5  h. Both states enable the measurement of real-time accumulation of ‘soluble’ versus ‘volatile&rsqu...
Source: Cancer Immunology, Immunotherapy - May 21, 2018 Category: Cancer & Oncology Source Type: research

How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions
AbstractMyeloid-derived suppressor cells (MDSC) are a heterogeneous group of mononuclear and polymorphonuclear myeloid cells, which are present at very low numbers in healthy subjects, but can expand substantially under disease conditions. Depending on disease type and stage, MDSC comprise varying amounts of immature and mature differentiation stages of myeloid cells. Validated unique phenotypic markers for MDSC are still lacking. Therefore, the functional analysis of these cells is of central importance for their identification and characterization. Various disease-promoting and immunosuppressive functions of MDSC are rep...
Source: Cancer Immunology, Immunotherapy - May 21, 2018 Category: Cancer & Oncology Source Type: research

Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma
ConclusionsAssociations with specificHLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 12, 2018 Category: Cancer & Oncology Source Type: research

Myeloid-derived suppressor cells (MDSCs) in patients with solid tumors: considerations for granulocyte colony-stimulating factor treatment
AbstractMyeloid-derived suppressor cells (MDSCs) have been shown to contribute to tumor escape from host immune surveillance and to cancer progression by production of tumor-promoting soluble factors. Granulocyte colony-stimulating factor (G-CSF) is a principle cytokine controlling granulocyte number. Recombinant human G-CSF (rhG-CSF) has become the main therapeutic agent for the treatment of neutropenia and prophylaxis of febrile neutropenia in cancer patients. However, we show here that rhG-CSF triggers accumulation of granulocytic and monocytic subsets. Consequently, we discuss the pharmacological use of granulopoiesis ...
Source: Cancer Immunology, Immunotherapy - May 10, 2018 Category: Cancer & Oncology Source Type: research

Cystatin F as a regulator of immune cell cytotoxicity
AbstractCysteine cathepsins are lysosomal peptidases involved in the regulation of innate and adaptive immune responses. Among the diverse processes, regulation of granule-dependent cytotoxicity of cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells during cancer progression has recently gained significant attention. The function of cysteine cathepsins is regulated by endogenous cysteine protease inhibitors —cystatins. Whereas other cystatins are generally cytosolic or extracellular proteins, cystatin F is present in endosomes and lysosomes and is thus able to regulate the activity of its target directly. It...
Source: Cancer Immunology, Immunotherapy - May 10, 2018 Category: Cancer & Oncology Source Type: research

VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival
In this study, 85 primary melanoma specimens were selected from pathology tissue archives and immunohistochemically stained for CD3, PD-1, PD-L1, and VISTA. Pearson ’s correlation coefficients identified associations in expression between VISTA and myeloid infiltrate (r = 0.28,p = 0.009) and the density of PD-1+ inflammatory cells (r = 0.31,p = 0.005). The presence of VISTA was associated with a significantly worse disease-specific survival in univariate analysis (hazard ratio = 3.57,p = 0.005) and multivariate analysis (hazard ratio&...
Source: Cancer Immunology, Immunotherapy - May 8, 2018 Category: Cancer & Oncology Source Type: research

Author Correction: Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin
This correction refers to ourShort Communication published inCancer Immunology Immunotherapy in the year 2012 [1]. It has come to our attention that some errors resulting from accidental oversight concerning incorrect deletion/replacement of temporary placeholder images during figure assembly and mounting occurred during the assembly of the “Intracellular Proteins” immunoblots presented in Fig. 1A and Fig. 1D. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 8, 2018 Category: Cancer & Oncology Source Type: research

Pushing the limits of immune-related response: a case of “extreme pseudoprogression”
We describe a case of pseudoprogression that pushes the limits of immune-related response criteria and challenges the boundaries and definitions set by trial protocols. A middle-aged man with conventional clear cell renal cell carcinoma (RCC) had received multiple prior systemic treatments including vascular endothelial growth factor receptor tyrosine kinase inhibitors, as well as multiple surgeries and radiotherapy treatments. He was eventually started on nivolumab —the anti-programmed death receptor-1 monoclonal antibody approved for the treatment of advanced RCC. Clinical deterioration was observed soon after a 10...
Source: Cancer Immunology, Immunotherapy - May 4, 2018 Category: Cancer & Oncology Source Type: research

Response to “Immune-mediated cholangitis: is it always nivolumab’s fault?”
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 26, 2018 Category: Cancer & Oncology Source Type: research

Role of MDA5 and interferon-I in dendritic cells for T cell expansion by anti-tumor peptide vaccines in mice
AbstractCytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role not only in antigen presentation but are critical in generating costimu...
Source: Cancer Immunology, Immunotherapy - April 25, 2018 Category: Cancer & Oncology Source Type: research

The binding of an anti-PD-1 antibody to Fc γRΙ has a profound impact on its biological functions
AbstractAntibodies targeting PD-1 have been demonstrated durable anti-cancer activity in certain cancer types. However, the anti-PD-1 antibodies are less or not efficacious in many situations, which might be attributed to co-expression of multiple inhibitory receptors or presence of immunosuppressive cells in the tumor microenvironment. Most of the anti-PD-1 antibodies used in clinical studies are of IgG4 isotype with the S228P mutation (IgG4S228P). The functional impact by the interaction of anti-PD-1 IgG4S228P antibody with Fc gamma receptors (Fc γRs) is poorly understood. To assess the effects, we generated a pair...
Source: Cancer Immunology, Immunotherapy - April 23, 2018 Category: Cancer & Oncology Source Type: research

Regulatory T cells control endothelial chemokine production and migration of T cells into intestinal tumors of APC min/+ mice
In conclusion, this study demonstrates that Treg reduce endothelial CXCL10 production, inhibit T-cell migration into tumors and that CXCR3 mediated signalling is crucial for lymphocyte accumulation in intestinal tumors. Thus, immunotherapy aimed at Treg depletion may be effective by increasing not only T effector cell activity, but also their accumulation in tumors. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 18, 2018 Category: Cancer & Oncology Source Type: research

Personalized cancer vaccines: adjuvants are important, too
AbstractTherapeutic cancer vaccines have shown limited clinical efficacy so far. Nevertheless, in the meantime, our understanding of immune cell function and the interactions of immune cells with growing tumors has advanced considerably. We are now in a position to invest this knowledge into the design of more powerful vaccines and therapy combinations aimed at increasing immunogenicity and decreasing tumor-induced immunosuppression. This review focuses essentially on peptide-based human vaccines. We will discuss two aspects that are critical for increasing their intrinsic immunogenicity: the selection of the antigen(s) to...
Source: Cancer Immunology, Immunotherapy - April 11, 2018 Category: Cancer & Oncology Source Type: research

Immune-mediated cholangitis: is it always nivolumab ’s fault?
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 5, 2018 Category: Cancer & Oncology Source Type: research

Interferon- α2b-induced STAT3 suppression in myeloid-derived suppressor cells in mycosis fungoides
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 4, 2018 Category: Cancer & Oncology Source Type: research

Induction of a central memory and stem cell memory phenotype in functionally active CD4 + and CD8 + CAR T cells produced in an automated good manufacturing practice system for the treatment of CD19 + acute lymphoblastic leukemia
In conclusion, partly automated GMP-generation of CAR T cells from critically small blood samples was f easible with a new stimulation protocol that leads to high functionality and expansion potential, balanced CD4/CD8 ratios and a conversion to a Tcm/Tscm phenotype. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 31, 2018 Category: Cancer & Oncology Source Type: research

Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer
AbstractImmunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. In these studies, 60% of stage IV melanoma DC-treated patients showed immunological responses corre...
Source: Cancer Immunology, Immunotherapy - March 29, 2018 Category: Cancer & Oncology Source Type: research

The role of myeloid derived suppressor cells in mycosis fungoides
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 24, 2018 Category: Cancer & Oncology Source Type: research

Depleted polymorphonuclear leukocytes in human metastatic liver reflect an altered immune microenvironment associated with recurrent metastasis
AbstractBackgroundHepatic immunity, normally protective against neoplasia, is subverted in colorectal liver metastasis (CRLM). Here, we compare the inflammatory microenvironment of CRLM-bearing liver tissue to donor liver.MethodsTwenty-five patients undergoing resection for CRLM were recruited, 13 of whom developed intrahepatic recurrence within 18 months. Biopsies were obtained from tumour and normal liver tissue adjacent to and distal from, the tumour. Donor liver biopsies were obtained during transplantation. Biopsies were cultured and conditioned media (CM) screened for 102 inflammatory mediators. Twelve of these were ...
Source: Cancer Immunology, Immunotherapy - March 23, 2018 Category: Cancer & Oncology Source Type: research

Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals
AbstractThe arsenal of cancer therapies has evolved to target T lymphocytes and restore their capacity to destroy tumor cells. T cells rely on diacylglycerol (DAG) to carry out their functions. DAG availability and signaling are regulated by the enzymes diacylglycerol kinase (DGK) α and ζ, whose excess function drives T cells into hyporesponsive states. Targeting DGKα is a promising strategy for coping with cancer; its blockade could reinstate T-cell attack on tumors while limiting tumor growth, due to positive DGKα functions in several oncogenic pathways. Here, we made a side-by-side comparison of t...
Source: Cancer Immunology, Immunotherapy - March 23, 2018 Category: Cancer & Oncology Source Type: research

Quantitative T-cell repertoire analysis of peripheral blood mononuclear cells from lung cancer patients following long-term cancer peptide vaccination
AbstractTherapeutic cancer peptide vaccination is an immunotherapy designed to elicit cytotoxic T-lymphocyte (CTL) responses in patients. A number of therapeutic vaccination trials have been performed, nevertheless there are only a few reports that have analyzed the T-cell receptors (TCRs) expressed on tumor antigen-specific CTLs. Here, we use next-generation sequencing (NGS) to analyze TCRs of vaccine-induced CTL clones and the TCR repertoire of bulk T cells in peripheral blood mononuclear cells (PBMCs) from two lung cancer patients over the course of long-term vaccine therapy. In both patients, vaccination with two epito...
Source: Cancer Immunology, Immunotherapy - March 22, 2018 Category: Cancer & Oncology Source Type: research

The novel deubiquitinase inhibitor b-AP15 induces direct and NK cell-mediated antitumor effects in human mantle cell lymphoma
AbstractThe first therapeutic proteasome inhibitor bortezomib has clinical efficacy in mantle cell lymphoma (MCL) which resulted in its incorporation in treatment algorithms for this disease. Impairment of proteasomal function by bortezomib is mediated via inhibition of the 20S core particle. However, proteasome function can also be modified by targeting upstream components of the ubiquitin –proteasome system. Recently, b-AP15 has been identified as a small molecule achieving proteasome inhibition by targeting the deubiquitinase (DUB) activity of the 19S regulatory subunit and was found to inhibit cancer cell growth ...
Source: Cancer Immunology, Immunotherapy - March 19, 2018 Category: Cancer & Oncology Source Type: research

Enhanced expression of PD-1 and other activation markers by CD4+ T cells of young but not old patients with metastatic melanoma
In conclusion, we show that CD4+ T cells of young melanoma patients show signs of activation, whereas these signs are less clear in CD4+ T cells of old patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 15, 2018 Category: Cancer & Oncology Source Type: research

Quantifying tumor-infiltrating immune cells from transcriptomics data
AbstractBy exerting pro- and anti-tumorigenic actions, tumor-infiltrating immune cells can profoundly influence tumor progression, as well as the success of anti-cancer therapies. Therefore, the quantification of tumor-infiltrating immune cells holds the promise to unveil the multi-faceted role of the immune system in human cancers and its involvement in tumor escape mechanisms and response to therapy. Tumor-infiltrating immune cells can be quantified from RNA sequencing data of human tumors using bioinformatics approaches. In this review, we describe state-of-the-art computational methods for the quantification of immune ...
Source: Cancer Immunology, Immunotherapy - March 14, 2018 Category: Cancer & Oncology Source Type: research

Cancer immunotherapy in patients with brain metastases
AbstractThe exclusion of “real-world” patients from registration clinical trials of cancer immunotherapy represents a significant emerging issue. For instance, a large fraction of cancer patients develops brain metastases during the course of the disease, but results from large prospective clinical trials investigating this considerable proportion of the cancer patient population are currently lacking. To provide a useful tool for the clinician in a “real-world” setting, we have reviewed the available literature regarding the safety and efficacy of immune check-point inhibitors in patients with canc...
Source: Cancer Immunology, Immunotherapy - March 8, 2018 Category: Cancer & Oncology Source Type: research

The non-small cell lung cancer immune landscape: emerging complexity, prognostic relevance and prospective significance in the context of immunotherapy
AbstractImmunotherapy of non-small cell lung cancer (NSCLC), by immune checkpoint inhibitors, has profoundly improved the clinical management of advanced disease. However, only a fraction of patients respond and no effective predictive factors have been defined. Here, we discuss the prospects for identification of such predictors of response to immunotherapy, by fostering an in-depth analysis of the immune landscape of NSCLC. The emerging picture, from several recent studies, is that the immune contexture of NSCLC lesions is a complex and heterogeneous feature, as documented by analysis for frequency, phenotype and spatial...
Source: Cancer Immunology, Immunotherapy - March 7, 2018 Category: Cancer & Oncology Source Type: research

Rituximab as a therapeutic option for patients with advanced melanoma
In conclusion, rituximab might be a therapeutic option for metastatic melanoma. However, further studies on rituximab among larger patient cohorts are warranted. Evaluation of therapy in an adjuvant setting or in combination with other systemic treatment might, therefore, be of particular interest. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 7, 2018 Category: Cancer & Oncology Source Type: research

Rational combinations of in vivo cancer antigen priming and adoptive T-cell therapy mobilize immune and clinical responses in terminal cancers
ConclusionsOur treatment protocol successfully demonstrated significant correlation between tumor-associated antigen-specific immune response and objective prolongation of survival. Whole-cell cancer antigen priming and adoptive T-cell therapy is, therefore, a highly feasible clinical model which can be easily replicated to positively influence outcome in end-stage malignancy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 6, 2018 Category: Cancer & Oncology Source Type: research

CD137L dendritic cells induce potent response against cancer-associated viruses and polarize human CD8 + T cells to Tc1 phenotype
This study shows that CD137L-DCs have a superior ability to activate T cells and to induce potent Tc1 responses against the cancer-causing viruses EBV and HBV which suggest CD137L-DCs as promising candidates for DC-based tumor immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 5, 2018 Category: Cancer & Oncology Source Type: research