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Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes

Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating lymphocytes (TILs) with significant clinical results. De...

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Autores principales: Zawidzka, Elizabeth M., Biavati, Luca, Thomas, Amy, Zanettini, Claudio, Marchionni, Luigi, Leone, Robert, Borrello, Ivan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491133/
https://www.ncbi.nlm.nih.gov/pubmed/37693379
http://dx.doi.org/10.1101/2023.08.28.555119
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author Zawidzka, Elizabeth M.
Biavati, Luca
Thomas, Amy
Zanettini, Claudio
Marchionni, Luigi
Leone, Robert
Borrello, Ivan
author_facet Zawidzka, Elizabeth M.
Biavati, Luca
Thomas, Amy
Zanettini, Claudio
Marchionni, Luigi
Leone, Robert
Borrello, Ivan
author_sort Zawidzka, Elizabeth M.
collection PubMed
description Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating lymphocytes (TILs) with significant clinical results. Despite these successes, the limitations of the current strategies are also emerging and novel approaches are needed. The bone marrow (BM) is an immunological niche that houses T cells with specificity for previously encountered antigens, including tumor-associated antigens from certain solid cancers. This study sought to improve our understanding of tumor-specific BM T cells in the context of solid tumors by comparing them with TILs, and to assess whether there is a rationale for using the BM as a source of T cells for ACT against solid malignancies. Herein, we demonstrate that T cells from the BM appear superior to TILs as a source of cells for cellular therapy. Specifically, they possess a memory-enriched phenotype and exhibit improved effector function, greater persistence within a tumor-bearing host, and the capacity for increased tumor infiltration. Taken together, these data provide a foundation for further exploring the BM as a source of tumor-specific T cells for ACT in solid malignancies.
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spelling pubmed-104911332023-09-09 Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes Zawidzka, Elizabeth M. Biavati, Luca Thomas, Amy Zanettini, Claudio Marchionni, Luigi Leone, Robert Borrello, Ivan bioRxiv Article Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating lymphocytes (TILs) with significant clinical results. Despite these successes, the limitations of the current strategies are also emerging and novel approaches are needed. The bone marrow (BM) is an immunological niche that houses T cells with specificity for previously encountered antigens, including tumor-associated antigens from certain solid cancers. This study sought to improve our understanding of tumor-specific BM T cells in the context of solid tumors by comparing them with TILs, and to assess whether there is a rationale for using the BM as a source of T cells for ACT against solid malignancies. Herein, we demonstrate that T cells from the BM appear superior to TILs as a source of cells for cellular therapy. Specifically, they possess a memory-enriched phenotype and exhibit improved effector function, greater persistence within a tumor-bearing host, and the capacity for increased tumor infiltration. Taken together, these data provide a foundation for further exploring the BM as a source of tumor-specific T cells for ACT in solid malignancies. Cold Spring Harbor Laboratory 2023-08-29 /pmc/articles/PMC10491133/ /pubmed/37693379 http://dx.doi.org/10.1101/2023.08.28.555119 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Zawidzka, Elizabeth M.
Biavati, Luca
Thomas, Amy
Zanettini, Claudio
Marchionni, Luigi
Leone, Robert
Borrello, Ivan
Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes
title Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes
title_full Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes
title_fullStr Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes
title_full_unstemmed Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes
title_short Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes
title_sort tumor-specific cd8(+) t cells from the bone marrow resist exhaustion and exhibit increased persistence in tumor-bearing hosts as compared to tumor infiltrating lymphocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491133/
https://www.ncbi.nlm.nih.gov/pubmed/37693379
http://dx.doi.org/10.1101/2023.08.28.555119
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