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Combinatorial Approaches With Checkpoint Inhibitors to Enhance Anti-tumor Immunity.

ABSTRACT: Treatment of cancer patients has been recently revolutionized by the application of various immunotherapeutics. However, the response rates are still limited ranging between approximately 20 and 40% suggesting that combinations of immunotherapy with conventional treatment, like chemotherapy, radiation, epigenetic modulators, targeted therapies using small molecules as well as other (immuno) therapeutics, might be an option to increase systemic anti-tumor immunity. It is postulated that different non-immune based therapies in combination with immunotherapies could reprogram the immune suppressive tumor microenvironment and enhance the immunogenicity of tumor cells leading to an improved therapeutic efficacy and a better patients' outcome. Despite there exist various examples of increased objective responses achieved by adding these different therapies to immunotherapies, strategies for rational and evidence-based design of checkpoint inhibitor combinations to maximize the clinical benefit for patients are urgently required. Therefore, the main purpose of this review is to summarize recent results obtained from experimental models and clinical trials to enhance tumor immunogenicity by combining immunotherapy with other therapeutic options to maximize patients' outcome and minimize adverse events.

SUBMITTER: Seliger B

PROVIDER: S-EPMC6538766 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Combinatorial Approaches With Checkpoint Inhibitors to Enhance Anti-tumor Immunity.

Seliger Barbara B

Frontiers in immunology 20190522

Treatment of cancer patients has been recently revolutionized by the application of various immunotherapeutics. However, the response rates are still limited ranging between approximately 20 and 40% suggesting that combinations of immunotherapy with conventional treatment, like chemotherapy, radiation, epigenetic modulators, targeted therapies using small molecules as well as other (immuno) therapeutics, might be an option to increase systemic anti-tumor immunity. It is postulated that different ...[more]

PMID: 31178856

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Project description:Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15-60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical biomarker for ICI response in patients is immune-related adverse event (IRAE) onset.IRAEs are thought to represent bystander effects from activated T-cells and it is plausible that patients responding to ICIs would have greater likelihood of autoimmune toxicities (e.g. due to a more competent/treatment-responsive immune system, or cross-reactivity between tumor and host tissue). Earlier studies in melanoma patients however, suggested no association between IRAE onset and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody efficacy. In contrast, a growing body of literature suggests IRAE onset is predictive of anti-programmed cell death protein 1 (PD-1) and anti-PD-L1 antibody response across a variety of solid tumors. Most of these studies report that patients who experienced IRAEs demonstrate marked improvements in progression-free survival, overall survival and overall response rate compared to those lacking toxicity.Key questions regarding the association between IRAE onset and ICI efficacy remain. The most pertinent of these involve whether the association is only relevant for patients treated with anti-PD-1 and anti-PD-L1 antibodies and whether IRAE site, severity, timing of onset and management influence ICI efficacy. Herein, we discuss the seminal studies which have begun to address these questions and have shaped the narrative about the predictive value of IRAE onset for patients on ICIs, in this review.

Dataset Information

Combinatorial Approaches With Checkpoint Inhibitors to Enhance Anti-tumor Immunity.

Publications

Combinatorial Approaches With Checkpoint Inhibitors to Enhance Anti-tumor Immunity.

Similar Datasets

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