Journal for Immunotherapy of Cancer 
This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.
This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial
AbstractProgrammed cell death protein 1 (PD-1) blockade is only effective in a minority of patients, prompting the search for combinatorial therapies that increase responses. Identifying effective combinations requires lengthy testing and so far has shown few successes. To accelerate progress Voorwerk and colleagues (Nat Med. 25(6):920-8, 2019) used an adaptive trial design to compare 4 short-course therapies (radiotherapy, cyclophosphamide, cisplatin and doxorubicin) for their ability to improve the tumor immune microenvironment and enhance responses to subsequent PD-1 blockade in women with metastatic triple negative bre...
Source: Journal for Immunotherapy of Cancer - November 20, 2019 Category: Cancer & Oncology Source Type: research
Peritumoral administration of DRibbles-pulsed antigen-presenting cells enhances the antitumor efficacy of anti-GITR and anti-PD-1 antibodies via an antigen presenting independent mechanism
ConclusionsOverall, these results demonstrate that peritumoral DR-pulsed-BMC/DC administration synergizes with GITR agonist and PD-1 blockade to locally modulate and sustain tumor effector T-cell responses independently of T cell priming and perhaps through innate inflammatory modulations mediated by the DRibbles adjuvant. We offer a unique approach to modify the tumor microenvironment to benefit T-cell-targeted immunotherapies. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 19, 2019 Category: Cancer & Oncology Source Type: research
Calreticulin exposure correlates with robust adaptive antitumor immunity and favorable prognosis in ovarian carcinoma patients
ConclusionsOur data indicate that CALR levels in primary and metastatic HGSC samples have robust prognostic value linked to the activation of clinically-relevant innate and adaptive anticancer immune responses. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 19, 2019 Category: Cancer & Oncology Source Type: research
Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment
ConclusionsOnly 3 out of 612 non-silent mutations encoded for neoantigens that were detectable by MS. Although MS has sensitivity limits and biases, and likely underestimated the true neoantigen burden, this established a lower bound of the percentage of non-silent mutations that encode for presented neoantigens, which may be as low as 0.5%. This could be a reason for the poor responses of non-hypermutated CRCs to immune checkpoint inhibitors. MEK-inhibitors recently failed to improve checkpoint-inhibitor efficacy in CRC and the observed lack of HLA upregulation or improved peptide presentation may explain this. (Source: J...
Source: Journal for Immunotherapy of Cancer - November 17, 2019 Category: Cancer & Oncology Source Type: research
A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer
ConclusionThus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 14, 2019 Category: Cancer & Oncology Source Type: research
Mechanisms regulating PD-L1 expression on tumor and immune cells
ConclusionsMultiple cytokines found in an immune-reactive TME may induce PD-L1 expression on tumor and/or immune cells through distinct signaling mechanisms. Factors driving constitutive PD-L1 expression were not identified in this study. Understanding complex mechanisms underlying PD-L1 display in the TME may allow treatment approaches mitigating expression of this immunosuppressive ligand, to enhance the impact of PD-1 blockade. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 14, 2019 Category: Cancer & Oncology Source Type: research
Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors
AbstractAlthough immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15 –60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical bioma...
Source: Journal for Immunotherapy of Cancer - November 14, 2019 Category: Cancer & Oncology Source Type: research
The density and spatial tissue distribution of CD8 + and CD163 + immune cells predict response and outcome in melanoma patients receiving MAPK inhibitors
ConclusionsAnalysis of the spatially constrained distribution of CD8+ and CD163+ cells, representative of the opposite circuits of antitumor vs protumor immunity, respectively, may assist in identifying melanoma patients with improved response and better outcome upon treatment with MAPK inhibitors. These data underline the role of endogenous immune microenvironment in predisposing metastatic melanoma patients to benefit from therapies targeting driver-oncogenic pathways. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 14, 2019 Category: Cancer & Oncology Source Type: research
Dual checkpoint inhibitor-associated eosinophilic enteritis
ConclusionsImmune checkpoint inhibition can trigger inflammation in virtually any organ in the body, leading to diverse clinical manifestations. To our knowledge, this is the first case report of eosinophilic enteritis due to ipilimumab plus nivolumab. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 14, 2019 Category: Cancer & Oncology Source Type: research
CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma
AbstractDespite remarkable success in the treatment of hematological malignancies, CAR T-cell therapies for solid tumors have floundered, in large part due to local immune suppression and the effects of prolonged stimulation leading to T-cell dysfunction and exhaustion. One mechanism by which gliomas and other cancers can hamper CAR T cells is through surface expression of inhibitory ligands such as programmed cell death ligand 1 (PD-L1). Using the CRIPSR-Cas9 system, we created universal CAR T cells resistant to PD-1 inhibition through multiplexed gene disruption of endogenous T-cell receptor (TRAC), beta-2 microglobulin ...
Source: Journal for Immunotherapy of Cancer - November 13, 2019 Category: Cancer & Oncology Source Type: research
Long-term survival without graft-versus-host-disease following infusion of allogeneic myeloma-specific V β T cell families
ConclusionsThese data demonstrate that a transplantation protocol involving only selective tumor-reactive donor T cell families is an effective immunotherapy and results in long-term survival in a mouse model of human MM. The results highlight the need to develop similar ATCT strategies for MM patients that result in enhanced survival without symptoms of GvHD. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 13, 2019 Category: Cancer & Oncology Source Type: research
Blood-derived dendritic cell vaccinations induce immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer
ConclusionsImmunotherapy with blood-derived DC subsets was feasible and safe and induced functional antigen-specific T cells. The presence of functional antigen-specific T cells correlated with an improved clinical outcome.Trial registrationClinicalTrials.gov identifierNCT02692976, registered 26 February 2016, retrospectively registered. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 13, 2019 Category: Cancer & Oncology Source Type: research
EZH2 negatively regulates PD-L1 expression in hepatocellular carcinoma
ConclusionsThe epigenetic modificator EZH2 can suppress the expression of immune checkpoint inhibitor PD-L1 by directly upregulating the promoter H3K27me3 levels ofCD274 andIRF1 in hepatoma cells, and might serve as a potential therapeutic target for combination of immunotherapy for immune-activated HCC. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 13, 2019 Category: Cancer & Oncology Source Type: research
Anti-TNF, a magic bullet in cancer immunotherapy?
AbstractImmune checkpoint blockers (ICB) have revolutionized cancer therapy. However, complete response is observed in a minority of patients and most patients develop immune-related adverse events (irAEs). These include colitis, which can be treated with anti-tumor necrosis factor (TNF) antibodies such as Infliximab. In a recent issue of the Journal for ImmunoTherapy of Cancer, Badran et al. reported that co-administering Infliximab together with ICB to five cancer patients prevents colitis recurrence, with four of them exhibiting overall disease stability. The basis for this treatment strategy stemmed from our pre-clinic...
Source: Journal for Immunotherapy of Cancer - November 13, 2019 Category: Cancer & Oncology Source Type: research
Development and validation of an immune checkpoint-based signature to predict prognosis in nasopharyngeal carcinoma using computational pathology analysis
ConclusionsWe determined the expression status of nine immune checkpoints consistent with 13 features in NPC and further constructed an ICS prognostic model, which might add prognostic value to the TNM staging system. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 12, 2019 Category: Cancer & Oncology Source Type: research
