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Small molecule immunomodulation: the tumor microenvironment and overcoming immune escape
AbstractImmunotherapy has led to a paradigm shift in the treatment of many advanced malignancies. Despite the success in treatment of tumors like non-small cell lung cancer (NSCLC) and melanoma, checkpoint inhibition-based immunotherapy has limitations. Many tumors, such as pancreatic cancer, are less responsive to checkpoint inhibitors, where patients tend to have a limited duration of benefit and where clinical responses are more robust in patients who are positive for predictive biomarkers. One of the critical factors that influence the efficacy of immunotherapy is the tumor microenvironment (TME), which contains a hete...
Source: Journal for Immunotherapy of Cancer - August 21, 2019 Category: Cancer & Oncology Source Type: research

The complex relationship between body mass index and response to immune checkpoint inhibition in metastatic melanoma patients
AbstractDespite major improvements in combatting metastatic melanoma since the advent of immunotherapy, the overall survival for patients with advanced disease remains low. Recently, there is a growing number of reports supporting an “obesity paradox,” in which patients who are overweight or mildly obese may exhibit a survival benefit in patients who received immune checkpoint inhibitors. We studied the relationship between body mass index and progression-free survival and overall survival in a cohort of 423 metastatic melan oma patients receiving immunotherapy, enrolled and prospectively followed up in the NYU Interdi...
Source: Journal for Immunotherapy of Cancer - August 18, 2019 Category: Cancer & Oncology Source Type: research

The great debate at “Immunotherapy Bridge 2018”, Naples, November 29th, 2018
Discussion of these important topics are summarised in this report. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 14, 2019 Category: Cancer & Oncology Source Type: research

PD-L1 blockade engages tumor-infiltrating lymphocytes to co-express targetable activating and inhibitory receptors
ConclusionsThis study shows the presence of T cell subsets in the tumor micro-environment expressing both activating and inhibitory receptors. These TAI cells can be targeted by combined immunotherapy leading to improved survival. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 13, 2019 Category: Cancer & Oncology Source Type: research

Safety, tolerability, pharmacokinetics, and pharmacodynamics of the afucosylated, humanized anti-EPHA2 antibody DS-8895a: a first-in-human phase I dose escalation and dose expansion study in patients with advanced solid tumors
ConclusionsTwenty mg/kg DS-8895a infused intravenously every 2  weeks was generally safe and well tolerated in patients (n = 21) with advanced solid tumors. The exposure of DS-8895a seemed to increase dose-dependently and induce activated NK cells.Trial registrationPhase 1 Study of DS-8895a in patients with advanced solid tumors (NCT02004717; 7 November 2013 to 2 February 2017); retrospectively registered on 9 December 2013. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 13, 2019 Category: Cancer & Oncology Source Type: research

Indocyanine green and poly I:C containing  thermo-responsive liposomes used in immune-photothermal therapy prevent cancer growth and metastasis
ConclusionThese results demonstrated the potential usage of a piTRL with laser irradiation for immuno-photothermal therapy against various types of cancer and their metastases. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 13, 2019 Category: Cancer & Oncology Source Type: research

Combination immunotherapy and radiotherapy causes an abscopal treatment response in a mouse model of castration resistant prostate cancer
ConclusionsThese data provide preclinical evidence for the use of iRT targeting PD-1 and PD-L1 in the treatment of CRPC. Immune checkpoint inhibition combined with radiotherapy treats CPRC with significant increases in median survival compared to drug alone: 70% longer for anti-PD-1 and 130% for anti-PD-L1, and with an abscopal treatment effect.PrecisCastration-resistant prostate cancer in a wild-type mouse model is successfully treated by X-ray radiotherapy combined with PD-1 or PD-L1 immune checkpoint inhibition, demonstrating significantly increased median overall survival and robust local and abscopal treatment respons...
Source: Journal for Immunotherapy of Cancer - August 13, 2019 Category: Cancer & Oncology Source Type: research

Immune microenvironment modulation unmasks therapeutic benefit of radiotherapy and checkpoint inhibition
ConclusionsOverall, this study demonstrates that modulation of the immunosuppressive TIME is required to unlock the benefits of ICIs and radiotherapy to induce immunologic rejection of treatment-refractory established solid tumors. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 12, 2019 Category: Cancer & Oncology Source Type: research

Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1
ConclusionThe new HSV-1 based platform described provides a potent and versatile approach to developing new oncolytic immunotherapies for clinical use. Each of the modifications employed was demonstrated to aid in optimizing the potential of the virus to both directly kill tumors and to lead to systemic therapeutic benefit. For clinical use, these viruses are expected to be most effective in combination with other anti-cancer agents, in particular PD1/L1-targeted immune checkpoint blockade. The first virus from this program (expressing GALV-GP-R− and hGM-CSF) has entered clinical development alone and in combination with...
Source: Journal for Immunotherapy of Cancer - August 9, 2019 Category: Cancer & Oncology Source Type: research

Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF- κB signaling
ConclusionsCRC cell-secreted CCL20 can recruit Tregs to promote chemoresistance via FOXO1/CEBPB/NF- κB signaling, indicating that the FOXO1/CEBPB/NF-κB/CCL20 axis might provide a promising target for CRC treatment. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 7, 2019 Category: Cancer & Oncology Source Type: research

Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution
ConclusionsThis case series underscores the value of targeted immunotherapy in treating angiosarcoma. It also identifies genetic heterogeneity of cutaneous angiosarcomas and discusses specific genetic findings that may explain reported benefits from immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 7, 2019 Category: Cancer & Oncology Source Type: research

Correction to: IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells
. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 7, 2019 Category: Cancer & Oncology Source Type: research

Immunogenicity of pembrolizumab in patients with advanced tumors
ConclusionsThe incidence of TE (neutralizing positive) ADAs against pembrolizumab was low in patients with advanced tumors. Furthermore, immunogenicity did not appear to have any clinically relevant effects on the exposure, safety, or efficacy of pembrolizumab.Trial registrationClinicalTrials.gov,NCT01295827 (February 15, 2011),NCT01704287 (October 11, 2012),NCT01866319 (May 31, 2013),NCT01905657 (July 23, 2013),NCT02142738 (May 20, 2014),NCT01848834 (May 8, 2013),NCT02255097 (October 2, 2014),NCT02460198 (June 2, 2015),NCT01953692 (October 1, 2013),NCT02453594 (May 25, 2015),NCT02256436 (October 3, 2014),NCT02335424 (Janu...
Source: Journal for Immunotherapy of Cancer - August 7, 2019 Category: Cancer & Oncology Source Type: research

miR-448 targets IDO1 and regulates CD8 + T cell response in human colon cancer
ConclusionOur findings indicated that IDO1 suppressed the CD8+ T cell response in colon cancer. miR-448, as a tumor-suppressive miRNA, enhanced the CD8+ T cell response by inhibiting IDO1 expression. The results provide a theoretical basis for the development of new immunotherapy for the treatment of colon cancer. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 6, 2019 Category: Cancer & Oncology Source Type: research

PD-1 silencing impairs the anti-tumor function of chimeric antigen receptor modified T cells by inhibiting proliferation activity
ConclusionThese results suggest that PD-1 might play an important role in maintaining the proper proliferation and differentiation of T cells, and PD-1 silencing would impair T cells ’ anti-tumor function by inhibiting their proliferation activity. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - August 6, 2019 Category: Cancer & Oncology Source Type: research