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CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape

Chimeric antigen receptor (CAR) T cell therapies have demonstrated remarkable efficacy for the treatment of hematological malignancies. However, in patients with solid tumors, objective responses to CAR-T cell therapy remain sporadic and transient. A major obstacle for CAR-T cells is the intrinsic a...

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Autores principales: Rodriguez-Garcia, Alba, Palazon, Asis, Noguera-Ortega, Estela, Powell, Daniel J., Guedan, Sonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311654/
https://www.ncbi.nlm.nih.gov/pubmed/32625204
http://dx.doi.org/10.3389/fimmu.2020.01109
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author Rodriguez-Garcia, Alba
Palazon, Asis
Noguera-Ortega, Estela
Powell, Daniel J.
Guedan, Sonia
author_facet Rodriguez-Garcia, Alba
Palazon, Asis
Noguera-Ortega, Estela
Powell, Daniel J.
Guedan, Sonia
author_sort Rodriguez-Garcia, Alba
collection PubMed
description Chimeric antigen receptor (CAR) T cell therapies have demonstrated remarkable efficacy for the treatment of hematological malignancies. However, in patients with solid tumors, objective responses to CAR-T cell therapy remain sporadic and transient. A major obstacle for CAR-T cells is the intrinsic ability of tumors to evade immune responses. Advanced solid tumors are largely composed of desmoplastic stroma and immunosuppressive modulators, and characterized by aberrant cell proliferation and vascularization, resulting in hypoxia and altered nutrient availability. To mount a curative response after infusion, CAR-T cells must infiltrate the tumor, recognize their cognate antigen and perform their effector function in this hostile tumor microenvironment, to then differentiate and persist as memory T cells that confer long-term protection. Fortunately, recent advances in synthetic biology provide a wide set of tools to genetically modify CAR-T cells to overcome some of these obstacles. In this review, we provide a comprehensive overview of the key tumor intrinsic mechanisms that prevent an effective CAR-T cell antitumor response and we discuss the most promising strategies to prevent tumor escape to CAR-T cell therapy.
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spelling pubmed-73116542020-07-02 CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape Rodriguez-Garcia, Alba Palazon, Asis Noguera-Ortega, Estela Powell, Daniel J. Guedan, Sonia Front Immunol Immunology Chimeric antigen receptor (CAR) T cell therapies have demonstrated remarkable efficacy for the treatment of hematological malignancies. However, in patients with solid tumors, objective responses to CAR-T cell therapy remain sporadic and transient. A major obstacle for CAR-T cells is the intrinsic ability of tumors to evade immune responses. Advanced solid tumors are largely composed of desmoplastic stroma and immunosuppressive modulators, and characterized by aberrant cell proliferation and vascularization, resulting in hypoxia and altered nutrient availability. To mount a curative response after infusion, CAR-T cells must infiltrate the tumor, recognize their cognate antigen and perform their effector function in this hostile tumor microenvironment, to then differentiate and persist as memory T cells that confer long-term protection. Fortunately, recent advances in synthetic biology provide a wide set of tools to genetically modify CAR-T cells to overcome some of these obstacles. In this review, we provide a comprehensive overview of the key tumor intrinsic mechanisms that prevent an effective CAR-T cell antitumor response and we discuss the most promising strategies to prevent tumor escape to CAR-T cell therapy. Frontiers Media S.A. 2020-06-17 /pmc/articles/PMC7311654/ /pubmed/32625204 http://dx.doi.org/10.3389/fimmu.2020.01109 Text en Copyright © 2020 Rodriguez-Garcia, Palazon, Noguera-Ortega, Powell and Guedan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Rodriguez-Garcia, Alba
Palazon, Asis
Noguera-Ortega, Estela
Powell, Daniel J.
Guedan, Sonia
CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
title CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
title_full CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
title_fullStr CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
title_full_unstemmed CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
title_short CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
title_sort car-t cells hit the tumor microenvironment: strategies to overcome tumor escape
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311654/
https://www.ncbi.nlm.nih.gov/pubmed/32625204
http://dx.doi.org/10.3389/fimmu.2020.01109
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