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Tumor microenvironment-derived S100A8/A9 is a novel prognostic biomarker for advanced melanoma patients and during immunotherapy with anti-PD-1 antibodies
ConclusionsThe tumor microenvironment-associated protein S100A8/A9 serves as a novel prognostic marker for metastasis and survival of metastatic melanoma patients and predicts response to immunotherapy with pembrolizumab. These data underscore the significance of tumor microenvironment-derived factors as suitable biomarkers for melanoma. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 4, 2019 Category: Cancer & Oncology Source Type: research

A phase Ib study of utomilumab (PF-05082566) in combination with mogamulizumab in patients with advanced solid tumors
ConclusionsThe combination of utomilumab/mogamulizumab was safe and tolerable, and may be suitable for evaluation in settings where CCR4-expressing Tregs are suppressing anticancer immunity.Trial registrationClinicalTrials.gov identifier:NCT02444793. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 3, 2019 Category: Cancer & Oncology Source Type: research

Tumor microenvironment dictates regulatory T cell phenotype: Upregulated immune checkpoints reinforce suppressive function
ConclusionsWe demonstrate that the TME confers a suppressive function on Treg cells by upregulating IC-molecule expression. Targeting IC-molecules, including PD-1, on Treg cells may be effective for cancer treatment. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 3, 2019 Category: Cancer & Oncology Source Type: research

Functional characterization of the selective pan-allele anti-SIRP α antibody ADU-1805 that blocks the SIRPα–CD47 innate immune checkpoint
ConclusionsBlocking the SIRP α-CD47 interaction via SIRPα, while similarly efficacious in vitro, differentiates ADU-1805 from CD47-targeting agents with respect to safety and absence of inhibition of T-cell activation. The data presented herein support further advancement of ADU-1805 towards clinical development. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 3, 2019 Category: Cancer & Oncology Source Type: research

Incidence rates of immune-related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI: a systematic review and meta-analysis
ConclusionThis meta-analysis summarizes the incidence rates of irAEs in patients with advanced solid tumours treated with NIVO or NIVO+IPI, and uncovers their correlations with ORR across multiple neoplasms. These findings highlight the potential of irAE to reflect response to NIVO or NIVO+IPI. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 3, 2019 Category: Cancer & Oncology Source Type: research

Rapid and sustained response to immune checkpoint inhibition in cutaneous squamous cell carcinoma after allogenic hematopoietic cell transplant for s ézary syndrome
ConclusionThis is the first case to our knowledge of rapid and durable response of both cSCC and CTCL to immune checkpoint inhibition after allo-HCT. Although this report highlights the potential for significant response to this class of medication, further studies are required to confirm the efficacy and safety of this approach in patients with CTCL after allo-HCT given the potential concern of GVHD. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 3, 2019 Category: Cancer & Oncology Source Type: research

Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study
AbstractBackgroundParaneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy.MethodsWe included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed b...
Source: Journal for Immunotherapy of Cancer - December 2, 2019 Category: Cancer & Oncology Source Type: research

Multiple nivolumab-induced CNS demyelination with spontaneous resolution in an asymptomatic metastatic melanoma patient
ConclusionWe report the first case of a melanoma patient with an asymptomatic and spontaneously reversible central nervous system demyelination following nivolumab immunotherapy. This case highlights the need for better recognition of such atypical and rare neurological toxicities which could be mistaken for progressive brain metastases. Early recognition and appropriate management are crucial to reduce severity and duration of these toxicities, especially for patients with less favourable evolution. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 1, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Pericardial effusion under nivolumab: case-reports and review of the literature
Following publication of the original article [1], the authors reported that authors ’ given and family names haven been incorrectly tagged. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 1, 2019 Category: Cancer & Oncology Source Type: research

Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge 2018” (28–29 November, 2018, Naples, Italy)
AbstractImmunotherapy is now widely established as a potent and effective treatment option across several types of cancer. However, there is increasing recognition that not all patients respond to immunotherapy, focusing attention on the immune contexture of the tumor microenvironment (TME), drivers of the immune response and mechanisms of tumor resistance to immunity. The development of novel immunotherapeutics and their use in combination with checkpoint inhibitors and other standard of care and novel treatment modalities is an area of particular attention across several tumor types, including melanoma, lung, ovarian, br...
Source: Journal for Immunotherapy of Cancer - November 28, 2019 Category: Cancer & Oncology Source Type: research

Angiogenesis and immune checkpoint inhibitors as therapies for hepatocellular carcinoma: current knowledge and future research directions
AbstractHepatocellular carcinoma (HCC) is the second deadliest cancer worldwide, due to its high incidence and poor prognosis. Frequent initial presentation at advanced stages along with impaired liver function limit the use of a broad therapeutic arsenal in patients with HCC. Although main HCC oncogenic drivers have been deciphered in recent years (TERT, TP53, CTNNB1 mutations, miR122 and CDKN2A silencing), therapeutic applications derived from this molecular knowledge are still limited. Given its high vascularization and immunogenicity, antiangiogenics and immune checkpoint inhibitors (ICI), respectively, are two therape...
Source: Journal for Immunotherapy of Cancer - November 28, 2019 Category: Cancer & Oncology Source Type: research

PD1 Hi CD8 + T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma
ConclusionThe current study unveils the unique features of PD1Hi CD8+ exhausted T cells in HCC, and also suggests that exhausted T cells could act as a biomarker to select the most care-demanding patients for tailored therapies. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 28, 2019 Category: Cancer & Oncology Source Type: research

Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients
ConclusionsOur study provides evidence that soluble immune checkpoint-related proteins may associate with advanced disease, recurrence and survival in ccRCC patients, which highlights the prognostic values of soluble immune checkpoint-related proteins. Future independent validation in prospective studies is warranted. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 28, 2019 Category: Cancer & Oncology Source Type: research

Longitudinal immune characterization of syngeneic tumor models to enable model selection for immune oncology drug discovery
ConclusionsTaken together, this dataset will provide a framework for characterization and enable the selection of the optimal models for immunotherapy combinations and generate potential biomarkers for clinical evaluation in identifying responders and non-responders to immunotherapy combinations. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 27, 2019 Category: Cancer & Oncology Source Type: research

MDM2 inhibitor APG-115 synergizes with PD-1 blockade through enhancing antitumor immunity in the tumor microenvironment
ConclusionOur results demonstrate that p53 activation mediated by APG-115 promotes antitumor immunity in the tumor microenvironment (TME) regardless of theTrp53 status of tumors per se. Instead, such an effect depends on p53 activation inTrp53 wild-type immune cells in the TME. Based on the data, a phase 1b clinical trial has been launched for the evaluation of APG-115 in combination with pembrolizumab in solid tumor patients including those withTP53mut tumors. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 27, 2019 Category: Cancer & Oncology Source Type: research