Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

The capacity of T cells to recognize and mount an immune response against tumor antigens depends on the large diversity of the T-cell receptor (TCR) repertoire generated in the thymus during the process of T-cell development. However, this process is dramatically impaired by immunological insults, s...

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Autores principales:	Antonella Cardinale, Carmen Dolores De Luca, Franco Locatelli, Enrico Velardi
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	immune reconstitution thymus immunotherapy TCR repertoire diversity T cells Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6c36bc8b1f474f11b82dd6e097a78eed
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spelling	oai:doaj.org-article:6c36bc8b1f474f11b82dd6e097a78eed2021-11-30T18:31:15ZThymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy1664-322410.3389/fimmu.2021.752042https://doaj.org/article/6c36bc8b1f474f11b82dd6e097a78eed2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.752042/fullhttps://doaj.org/toc/1664-3224The capacity of T cells to recognize and mount an immune response against tumor antigens depends on the large diversity of the T-cell receptor (TCR) repertoire generated in the thymus during the process of T-cell development. However, this process is dramatically impaired by immunological insults, such as that caused by cytoreductive cancer therapies and infections, and by the physiological decline of thymic function with age. Defective thymic function and a skewed TCR repertoire can have significant clinical consequences. The presence of an adequate pool of T cells capable of recognizing specific tumor antigens is a prerequisite for the success of cancer immunotherapy using checkpoint blockade therapy. However, while this approach has improved the chances of survival of patients with different types of cancer, a large proportion of them do not respond. The limited response rate to checkpoint blockade therapy may be linked to a suboptimal TCR repertoire in cancer patients prior to therapy. Here, we focus on the role of the thymus in shaping the T-cell pool in health and disease, discuss how the TCR repertoire influences patients’ response to checkpoint blockade therapy and highlight approaches able to manipulate thymic function to enhance anti-tumor immunity.Antonella CardinaleCarmen Dolores De LucaFranco LocatelliFranco LocatelliEnrico VelardiFrontiers Media S.A.articleimmune reconstitutionthymusimmunotherapyTCR repertoire diversityT cellsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune reconstitution thymus immunotherapy TCR repertoire diversity T cells Immunologic diseases. Allergy RC581-607
spellingShingle	immune reconstitution thymus immunotherapy TCR repertoire diversity T cells Immunologic diseases. Allergy RC581-607 Antonella Cardinale Carmen Dolores De Luca Franco Locatelli Franco Locatelli Enrico Velardi Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy
description	The capacity of T cells to recognize and mount an immune response against tumor antigens depends on the large diversity of the T-cell receptor (TCR) repertoire generated in the thymus during the process of T-cell development. However, this process is dramatically impaired by immunological insults, such as that caused by cytoreductive cancer therapies and infections, and by the physiological decline of thymic function with age. Defective thymic function and a skewed TCR repertoire can have significant clinical consequences. The presence of an adequate pool of T cells capable of recognizing specific tumor antigens is a prerequisite for the success of cancer immunotherapy using checkpoint blockade therapy. However, while this approach has improved the chances of survival of patients with different types of cancer, a large proportion of them do not respond. The limited response rate to checkpoint blockade therapy may be linked to a suboptimal TCR repertoire in cancer patients prior to therapy. Here, we focus on the role of the thymus in shaping the T-cell pool in health and disease, discuss how the TCR repertoire influences patients’ response to checkpoint blockade therapy and highlight approaches able to manipulate thymic function to enhance anti-tumor immunity.
format	article
author	Antonella Cardinale Carmen Dolores De Luca Franco Locatelli Franco Locatelli Enrico Velardi
author_facet	Antonella Cardinale Carmen Dolores De Luca Franco Locatelli Franco Locatelli Enrico Velardi
author_sort	Antonella Cardinale
title	Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy
title_short	Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy
title_full	Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy
title_fullStr	Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy
title_full_unstemmed	Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy
title_sort	thymic function and t-cell receptor repertoire diversity: implications for patient response to checkpoint blockade immunotherapy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6c36bc8b1f474f11b82dd6e097a78eed
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Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

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