Peripheral Blood-Based Biomarkers for Immune Checkpoint Inhibitors

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Abstract

As cancer immunotherapy using immune checkpoint inhibitors (ICIs) is rapidly evolving in clinical practice, it is necessary to identify biomarkers that will allow the selection of cancer patients who will benefit most or least from ICIs and to longitudinally monitor patients’ immune responses during treatment. Various peripheral blood-based immune biomarkers are being identified with recent advances in high-throughput multiplexed analytical technologies. The identification of these biomarkers, which can be easily detected in blood samples using non-invasive and repeatable methods, will contribute to overcoming the limitations of previously used tissue-based biomarkers. Here, we discuss the potential of circulating immune cells, soluble immune and inflammatory molecules, circulating tumor cells and DNA, exosomes, and the blood-based tumor mutational burden, as biomarkers for the prediction of immune responses and clinical benefit from ICI treatment in patients with advanced cancer.

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Cancer immunotherapy using checkpoint blockade

Jedd Wolchok, Antoni Ribas (2018)

The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte antigen-4 (CTLA-4) or the programmed death-1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the pre-existence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long lasting disease control, yet one third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon gamma signaling pathways. New generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.

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Record: found
Abstract: found
Article: not found

A guide to cancer immunotherapy: from T cell basic science to clinical practice

Alex Waldman, Jill Fritz, Michael Lenardo (2020)

The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation. We highlight clinical trials that demonstrate therapeutic efficacy and toxicities associated with each class of drug. Finally, we summarize emerging therapies and emphasize the yet to be elucidated questions and future promise within the field of cancer immunotherapy.

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Record: found
Abstract: found
Article: not found

Innate and adaptive immune cells in the tumor microenvironment.

Thomas Gajewski, Hans Schreiber, Yang-Xin Fu (2013)

Most tumor cells express antigens that can mediate recognition by host CD8(+) T cells. Cancers that are detected clinically must have evaded antitumor immune responses to grow progressively. Recent work has suggested two broad categories of tumor escape based on cellular and molecular characteristics of the tumor microenvironment. One major subset shows a T cell-inflamed phenotype consisting of infiltrating T cells, a broad chemokine profile and a type I interferon signature indicative of innate immune activation. These tumors appear to resist immune attack through the dominant inhibitory effects of immune system-suppressive pathways. The other major phenotype lacks this T cell-inflamed phenotype and appears to resist immune attack through immune system exclusion or ignorance. These two major phenotypes of tumor microenvironment may require distinct immunotherapeutic interventions for maximal therapeutic effect.