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Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma
ConclusionsIndividual immunotherapy panel markersCD274, PDCD1LG2, CD8A,IRF1 and a combinedL1/L2 mRNA levels show promising associations with melanoma immunotherapy outcome. The turnaround time of the test (2  h) and easy standardization of the platform makes this an attractive approach for further study in the search for predictive biomarkers for ICI. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 17, 2019 Category: Cancer & Oncology Source Type: research

Tertiary lymphoid organs in the inflammatory myopathy associated with PD-1 inhibitors
ConclusionsIn inflammatory myopathy associated with PD-1 inhibitors, CD8+ cells appear to predominantly destruct muscle fibers. The presence of lymphoid follicle-like structures and expression of PNAd and CCL21 on the endothelial cells suggest the tertiary lymphoid organs are formed, and involved in the leakage of lymphocytes. Thus, in the three cases examined, formation of the tertiary lymphoid organs is likely to play an important role in genesis of the PD-1 myopathy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 17, 2019 Category: Cancer & Oncology Source Type: research

Clinical and immune profiling for cancer of unknown primary site
ConclusionsThe survival outcome of CUP remains unsatisfactory. However, our clinical and immune profiling of CUP has revealed a potential to benefit from immunotherapy, with ICIs thus being a potential option for CUP treatment. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 12, 2019 Category: Cancer & Oncology Source Type: research

Therapeutic efficacy of a novel humanized antibody-drug conjugate recognizing plexin-semaphorin-integrin domain in the RON receptor for targeted cancer therapy
ConclusionH5B14-based ADCs targeting the RON PSI domain are superior in inducing RON internalization, leading to robust drug delivery and overall inhibition and eradication of tumors in multiple xenograft models. These findings warrant H5B14-based ADCs for clinical trials in the future. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 12, 2019 Category: Cancer & Oncology Source Type: research

Late-differentiated effector neoantigen-specific CD8+ T cells are enriched in peripheral blood of non-small cell lung carcinoma patients responding to atezolizumab treatment
ConclusionThis study demonstrates that neoantigen-specific T cells can be detected in peripheral blood in non-small cell lung cancer (NSCLC) patients during anti-PD-L1 therapy. Patients with an objective response had an enrichment of neoantigen-reactive T cells and these cells showed a phenotype that differed from patients without a response. These findings suggest the ex vivo identification, characterization, and longitudinal follow-up of rare tumor-specific differentiated effector neoantigen-specific T cells may be useful in predicting response to checkpoint blockade.Trial registrationPOPLAR trialNCT01903993. (Source: Jo...
Source: Journal for Immunotherapy of Cancer - September 11, 2019 Category: Cancer & Oncology Source Type: research

Recovery from secondary adrenal insufficiency in a patient with immune checkpoint inhibitor therapy induced hypophysitis
ConclusionsThis case documents the unusual recovery from secondary adrenal insufficiency in a patient who developed hypophysitis from immune checkpoint inhibitor therapy. Repeated pituitary hormone testing every three months for the first year after the development of hypophysitis may identify more patients with hypothalamic-pituitary-adrenal axis recovery. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 11, 2019 Category: Cancer & Oncology Source Type: research

Unchecked immunity: a unique case of sequential immune-related adverse events with Pembrolizumab
ConclusionsImmunosuppression resulted in clinical remission of each irAE, highlighting the importance of vigilance for autoimmune complications in patients treated with checkpoint inhibition, even after immunotherapy cessation. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 11, 2019 Category: Cancer & Oncology Source Type: research

Niclosamide, an antihelmintic drug, enhances efficacy of PD-1/PD-L1 immune checkpoint blockade in non-small cell lung cancer
ConclusionsAn enhancement of PD-L1 antibody by niclosamide was observed in inhibition of NSCLC growth in vitro and in vivo, which was involved in blockage of p-STAT3 binding to promoter of PD-L1 and finally downregulation of PD-L1 expression. These encourage the combination therapy of niclosamide and PD-1/PD-L1 blockade to be further studied in clinic. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 10, 2019 Category: Cancer & Oncology Source Type: research

Carboxyamidotriazole combined with IDO1-Kyn-AhR pathway inhibitors profoundly enhances cancer immunotherapy
ConclusionInhibitors of the IDO1-Kyn-AhR pathway could abolish the negative effects of CAI on CD8+ T cells and result in complementary and beneficial anti-tumor immune effects. The combination of CAI with 1-MT or DMF greatly augmented the ability of CD8+ T cells to kill malignant cells and showed a strong anti-cancer capability that was superior to that of either of the single agents was is comparable with that of anti-PD-1 antibody. The combinations of small molecules utilized in this study may serve as valuable new immunotherapy strategies for cancer treatment. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 10, 2019 Category: Cancer & Oncology Source Type: research

Intratumoral immunotherapy with TLR7/8 agonist MEDI9197 modulates the tumor microenvironment leading to enhanced activity when combined with other immunotherapies
ConclusionLocalized TLR7/8 agonism can enhance recruitment and activation of immune cells in tumors and polarize anti-tumor immunity towards a Th1 response. Moreover, we demonstrate that the anti-tumor effects of this TLR7/8 agonist can be enhanced through combination with checkpoint inhibitors and co-stimulatory agonists. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 10, 2019 Category: Cancer & Oncology Source Type: research

A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function
ConclusionOverall, we propose that TIGIT-based CSR can substantially enhance T-cell function and thus contribute to the improvement of engineered T cell-based immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 8, 2019 Category: Cancer & Oncology Source Type: research

Impact of antibiotic therapy on the development and response to treatment of immune checkpoint inhibitor-mediated diarrhea and colitis
ConclusionsWhereas antibiotic therapy appeared to be protective against IMDC onset, use of antibiotics, especially those with anaerobic activity, after ICI therapy was associated with increased risk of severe IMDC. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 4, 2019 Category: Cancer & Oncology Source Type: research

Anti-programmed cell death protein 1 (anti-PD1) immunotherapy induced autoimmune polyendocrine syndrome type II (APS-2): a case report and review of the literature
ConclusionThis is the first report of the full triad of APS-2 developing in a genetically susceptible individual at the age of 78 after treatment with an anti-PD1 agent. Although scarcely reported, a literature review of similar reports seems to indicate a predilection for this syndrome in patients with HLA-DR4 serotypes. HLA Class II typing is not routinely recommended, but may provide useful predictive information for patients at risk of poly-endocrinopathy even in patients without a relevant personal or family history. Additional studies are required to determine if such testing would be useful and/or cost effective. (S...
Source: Journal for Immunotherapy of Cancer - September 4, 2019 Category: Cancer & Oncology Source Type: research

Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors
ConclusionsHuMax-IL8 is safe and well-tolerated. Ongoing studies are evaluating the combination of IL-8 blockade and other immunotherapies.Trial registrationNCTN, NCT02536469. Registered 23 August 2015,https://clinicaltrials.gov/ct2/show/NCT02536469?term=NCT02536469&rank=1. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - September 4, 2019 Category: Cancer & Oncology Source Type: research

Biomaterial-based platforms for in situ dendritic cell programming and their use in antitumor immunotherapy
AbstractDendritic cells (DCs) are central players in the immune system, with an exquisite capacity to initiate and modulate immune responses. These functional characteristics have led to intense research on the development of DC-based immunotherapies, particularly for oncologic diseases. During recent decades, DC-based vaccines have generated very promising results in animal studies, and more than 300 clinical assays have demonstrated the safety profile of this approach. However, clinical data are inconsistent, and clear evidence of meaningful efficacy is still lacking. One of the reasons for this lack of evidence is the l...
Source: Journal for Immunotherapy of Cancer - September 3, 2019 Category: Cancer & Oncology Source Type: research