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A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund ’s adjuvant in melanoma patients
ConclusionsLPS and polyICLC are safe and effective vaccine adjuvants when combined with IFA. Contrary to the central hypothesis, IFA enhanced T cell responses to peptide vaccines when added to TLR agonists. Future studies will aim to understand mechanisms underlying the favorable effects with IFA.Trial registrationThe clinical trial Mel58 was performed with IRB (#15781) and FDA approval and is registered withClinicaltrials.gov on April 25, 2012 (NCT01585350). Patients provided written informed consent to participate. Enrollment started on June 24, 2012. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 26, 2019 Category: Cancer & Oncology Source Type: research

Response to targeted therapy or chemotherapy following immunotherapy in patients with gastrointestinal cancers - a case series
ConclusionWe postulate that the sequencing of immune checkpoint inhibitors prior to other forms of systemic therapy may potentially lead to an immunomodulatory effect in gastrointestinal cancers with potential improvement in response rates. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 26, 2019 Category: Cancer & Oncology Source Type: research

Pre-clinical investigation of the synergy effect of interleukin-12 gene-electro-transfer during partially irreversible electropermeabilization against melanoma
ConclusionsThe combination of pIL-12 GET and pIRE not only enhanced survival but could bring a curative effect in wild type mice. This two-step treatment, named Immune-Gene Electro-Therapy (IGET), led to a systemic activation of the adaptive immune system and the development of an anti-tumor immune memory. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 25, 2019 Category: Cancer & Oncology Source Type: research

Optimized fractionated radiotherapy with anti-PD-L1 and anti-TIGIT: a promising new combination
ConclusionEach fractionation scheme induced different lymphoid and myeloid responses as well as various modulations of PD-L1 and TIGIT expression. Furthermore, 3x8Gy was the most effective protocol when associated with anti-PD-L1 and anti-TIGIT. This is the first study combining RT and anti-TIGIT with promising results; further studies are warranted. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 24, 2019 Category: Cancer & Oncology Source Type: research

Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials
AbstractRecent phase 1 –2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lackin g. We aimed to comprehensively compare the efficacy and safety of different anti-PD-1 drugs, standard chemotherapy, and their combination therapy in RM-NPC. Adverse event (AE) and objective response rate (ORR) were assessed. The pooled incidence rates of grade 1–5/3–5 AEs were 74.1%/29.6, 54.2%/ 17.4,...
Source: Journal for Immunotherapy of Cancer - June 24, 2019 Category: Cancer & Oncology Source Type: research

Corrections to: Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature
Following publication of the original article [1], the authors reported an error in the Acknowledgments section. It should be read: ‘We are grateful to Mohsin Shah from the Department of Emergency Medicine at The University of Texas MD Anderson Cancer Center for assisting in study selection, and to Gregory F. Pratt from the Research Medical Library and Erica Goodoff, from the Department of Scientific Publications at The Univer sity of Texas MD Anderson Cancer Center for their valuable contributions. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 23, 2019 Category: Cancer & Oncology Source Type: research

Type I interferon suppresses tumor growth through activating the STAT3-granzyme B pathway in tumor-infiltrating cytotoxic T lymphocytes
ConclusionIFN-I induces STAT3 activation to activateGzmb expression to enhance CTL effector function to suppress tumor development. Human colorectal carcinoma may use down-regulation of IFNAR1 on CTLs to suppress CTL effector function to evade host cancer immunosurveillance. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 21, 2019 Category: Cancer & Oncology Source Type: research

Efficient identification of neoantigen-specific T-cell responses in advanced human ovarian cancer
ConclusionsOur study demonstrated the feasibility of efficiently identifying both CD4+ and CD8+ neoantigen-specific T-cells in EOC. Autologous lymphocytes genetically engineered with tumor antigen-specific TCR can be used to generate cells for use in the personalized adoptive T-cell transfer immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 19, 2019 Category: Cancer & Oncology Source Type: research

Tumor-associated macrophage expression of interferon regulatory Factor-8 (IRF8) is a predictor of progression and patient survival in renal cell carcinoma
AbstractTumor-associated macrophages have been well-characterized in solid malignancies, including renal cell carcinoma and generally correlate with poor prognosis. However, the molecular mechanisms which govern intratumoral macrophage behavior and patient outcome are unclear. Here, we investigated whether alterations in macrophage expression of the transcriptional regulator for myeloid commitment and function, interferon regulatory factor-8 (IRF8), could predict survival of clear cell renal cell carcinoma patients. Transcriptional analysis of publicly available data revealed elevated IRF8 expression was associated with pr...
Source: Journal for Immunotherapy of Cancer - June 19, 2019 Category: Cancer & Oncology Source Type: research

Tumor-targeted IL-12 combined with tumor resection yields a survival-favorable immune profile
ConclusionsttIL-12 when combined with surgery led to conversion to the IFN γHiCD8HiFOXP3LowCD33Low immune profile, eliminated relapse and metastasis, and prolonged overall survival. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 16, 2019 Category: Cancer & Oncology Source Type: research

B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors
ConclusionsThe degree of tumor infiltrating B cell content is not associated with response to anti-PD-1 inhibitors in melanoma. PD-1 inhibitors cause tumor shrinkage in murine cancer models even when B cells are absent or are depleted. PD-1 inhibitors are likely to be active in patients with impaired B cell function, such as patients undergoing B cell depletion with drugs including rituximab for conditions such as B cell malignancies or autoimmune disorders. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 13, 2019 Category: Cancer & Oncology Source Type: research

Metabolic stress in cancer cells induces immune escape through a PI3K-dependent blockade of IFN γ receptor signaling
ConclusionsThese data revealed a strong impact of metabolic stress on the presentation of tumor antigens by MHC class I and suggest that this type of tumor escape takes place at hypoxic areas even during times of active T cell immunity and IFNy release. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 12, 2019 Category: Cancer & Oncology Source Type: research

PD-1 signaling affects cristae morphology and leads to mitochondrial dysfunction in human CD8 + T lymphocytes
ConclusionsOur results suggest that mitochondria are the main targets of PD-1 inhibitory activity. PD-1 reprograms CD8+ T cell metabolism for efficient use of fatty acid oxidation; this mitochondrial phenotype might explain the long-lived phenotype of PD-1-engaged T cells. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 12, 2019 Category: Cancer & Oncology Source Type: research

Temporal changes within the (bladder) tumor microenvironment that accompany the therapeutic effects of the immunocytokine NHS-IL12
ConclusionsThese findings provide strong evidence that the systemic administration of an immunocytokine consisting of a tumor-targeting Ig through recognition of DNA and DNA-histone complexes coupled to muIL-12 can effectively target the bladder TME; this significantly reduces the myeloid cellular compartment and reverts an immunosuppressive to an immunopermissive TME, ultimately resulting in antitumor effects. These studies provide further rationale for the employment of NHS-IL12 as an immunomodulator and clinical immunotherapeutic for NMIBC. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 10, 2019 Category: Cancer & Oncology Source Type: research

CD45RA + CCR7 − CD8 T cells lacking co-stimulatory receptors demonstrate enhanced frequency in peripheral blood of NSCLC patients responding to nivolumab
ConclusionsThis study demonstrates that high numbers of peripheral CD8 T cells expressing differentiation markers and lacking co-stimulatory receptors at baseline are associated with response to nivolumab in NSCLC patients. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - June 7, 2019 Category: Cancer & Oncology Source Type: research