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Multiplex quantitative analysis of cancer-associated fibroblasts and immunotherapy outcome in metastatic melanoma
ConclusionsPretreatment CAF profiles are associated with melanoma immunotherapy outcome. Multiplex CAF analysis has potential as an objective companion diagnostic in immuno-oncology. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 22, 2019 Category: Cancer & Oncology Source Type: research

HERA-GITRL activates T cells and promotes anti-tumor efficacy independent of Fc γR-binding functionality
ConclusionIn this manuscript, we describe the development of HERA-GITRL, a true GITR agonist with a clearly defined mechanism of action. By clustering six receptor chains in a spatially well-defined manner, HERA-GITRL induces potent agonistic activity without being dependent on additional Fc γR-mediated crosslinking. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 18, 2019 Category: Cancer & Oncology Source Type: research

A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients
ConclusionsBased on the first real-world population-PK model of nivolumab, covariate analysis revealed a significant effect of gender, BSA, and albumin on nivolumab clearance. A clearance-response relationship was observed in NSCLC, with a non-significant trend in RCC, but not in melanoma. Individual pharmacology of nivolumab in NSCLC appears important and should be prospectively studied. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 18, 2019 Category: Cancer & Oncology Source Type: research

Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments
ConclusionsOur data implies that macrophage- initiated WNT signaling could play a significant role in the maintenance of stemness, and the resulting phenotypes of chemoresistance and invasiveness. Our results indicate paracrine WNT activation during CSC/M2 macrophages interaction constitutes a positive feedback loop that likely contributes to the more aggressive phenotype, which makes the WNT pathway a potential target to reduce the CSC and M2 macrophage compartments in the tumor microenvironment. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 18, 2019 Category: Cancer & Oncology Source Type: research

Oncolytic Maraba virus armed with tumor antigen boosts vaccine priming and reveals diverse therapeutic response patterns when combined with checkpoint blockade in ovarian cancer
ConclusionsOur findings point to a key hierarchical role for PD-1 signaling and adaptive immune resistance in the ovarian TME in determining the functional fate of tumor-specific CD8+ T cells, even in the context of robust therapy mediated anti-tumor immunity, as well as the ability of multiple unique patterns of therapeutic response to result in durable tumor control. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 16, 2019 Category: Cancer & Oncology Source Type: research

Diverse immunotherapies can effectively treat syngeneic brainstem tumors in the absence of overt toxicity
ConclusionsIt remains imperative to regard the brainstem with caution for immunotherapeutic intervention. Nonetheless, we show that further careful development of immunotherapies for pediatric brainstem tumors is warranted to harness the potential potency of anti-tumor immune responses, despite their possible toxicity within this anatomically sensitive location. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 16, 2019 Category: Cancer & Oncology Source Type: research

miR-34a as hub of T cell regulation networks
ConclusionsBy simultaneous targeting of 14 mRNAs miR-34a acts as major hub of T cell regulatory networks suggesting to utilize miR-34a as target of intervention towards a modulation of the immune responsiveness of T-cells in a broad tumor context. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 15, 2019 Category: Cancer & Oncology Source Type: research

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)
AbstractHead and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals – the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab – for the treatment of patients w...
Source: Journal for Immunotherapy of Cancer - July 14, 2019 Category: Cancer & Oncology Source Type: research

Molecular and metabolic pathways mediating curative treatment of a non-Hodgkin B cell lymphoma by Sindbis viral vectors and anti-4-1BB monoclonal antibody
ConclusionsOur study provides a novel, alternative method for B cell lymphoma treatment and describes a rationale to help translate SV vectors plus agonistic mAb into clinical applications. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 14, 2019 Category: Cancer & Oncology Source Type: research

Tumor mutational burden quantification from targeted gene panels: major advancements and challenges
AbstractTumor mutational burden (TMB), the total number of somatic coding mutations in a tumor, is emerging as a promising biomarker for immunotherapy response in cancer patients. TMB can be quantitated by a number of NGS-based sequencing technologies. Whole Exome Sequencing (WES) allows comprehensive measurement of TMB and is considered the gold standard. However, to date WES remains confined to research settings, due to high cost of the large genomic space sequenced. In the clinical setting, instead, targeted enrichment panels (gene panels) of various genomic sizes are emerging as the routine technology for TMB assessmen...
Source: Journal for Immunotherapy of Cancer - July 14, 2019 Category: Cancer & Oncology Source Type: research

Transgenerational transfer of gene-modified T cells
AbstractTumor immunotherapy using gene-modified T cells has already met with considerable success in the treatment of metastatic melanoma and B cell lymphoma. With improving patient prognoses, new questions arise. In particular, the long-term consequences of treatment among individuals of childbearing age could now be considered. Former patients can carry a cohort of transgenic memory T cells long after treatment has ceased and the effector T cell population has contracted. When patients become parents well after treatment is completed, expectant mothers may still pass transgenic T cells to their unborn children. Consequen...
Source: Journal for Immunotherapy of Cancer - July 14, 2019 Category: Cancer & Oncology Source Type: research

Tumor-released autophagosomes induces CD4 + T cell-mediated immunosuppression via a TLR2 –IL-6 cascade
ConclusionsHSP90 α on the surface of TRAPs programs the immunosuppressive functions of CD4+ T cells to promote tumor growth and metastasis. TRAPs or their membrane-bound HSP90 α represent important therapeutic targets to reverse cancer-associated immunosuppression and improve immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 11, 2019 Category: Cancer & Oncology Source Type: research

Tumor mutation burden and circulating tumor DNA in combined CTLA-4 and PD-1 antibody therapy in metastatic melanoma – results of a prospective biomarker study
ConclusionHigh TMB,>  50% decrease of cell-free DNA concentration, and undetectable ctDNA at first follow-up seem to be associated with response and overall survival under combined immunotherapy. The evaluation of ctDNA and cell-free DNA three weeks after treatment initiation may be suitable for early assessment of ef ficacy of immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 11, 2019 Category: Cancer & Oncology Source Type: research

Immune cell concentrations among the primary tumor microenvironment in colorectal cancer patients predicted by clinicopathologic characteristics and blood indexes
ConclusionAge, T stage, tumor location, CEA, monocytes, LMR and ApoA1 could reflect immune cells infiltrating the tumor microenvironment of CRC. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 11, 2019 Category: Cancer & Oncology Source Type: research

Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment
ConclusionClinicians prescribing ICIs should be aware that SOT recipients are at risk of transplant rejection as a result of T cell activation. Dd-cfDNA is a sensitive biomarker and should be further studied for early detection of transplant rejection. Immunological analysis of the kidney explant showed marked graft infiltration with alloreactive PD-1+ cytotoxic T cells that were saturated with nivolumab. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - July 11, 2019 Category: Cancer & Oncology Source Type: research