The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps

Remarkable progress has been made in the field of anti-tumor immunity, nevertheless many questions are still open. Thus, even though memory T cells have been implicated in long-term anti-tumor protection, particularly in prevention of cancer recurrence, the bases of their variable effectiveness in t...

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Autores principales:	Silvia Gitto, Ambra Natalini, Fabrizio Antonangeli, Francesca Di Rosa
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	immune checkpoint blockade memory T cells TRM bone marrow anti-tumor immunity Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/38e834c142604f07a966c5b64859bc5e
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spelling	oai:doaj.org-article:38e834c142604f07a966c5b64859bc5e2021-11-19T11:03:01ZThe Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps1664-322410.3389/fimmu.2021.755304https://doaj.org/article/38e834c142604f07a966c5b64859bc5e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.755304/fullhttps://doaj.org/toc/1664-3224Remarkable progress has been made in the field of anti-tumor immunity, nevertheless many questions are still open. Thus, even though memory T cells have been implicated in long-term anti-tumor protection, particularly in prevention of cancer recurrence, the bases of their variable effectiveness in tumor patients are poorly understood. Two types of memory T cells have been described according to their traffic pathways: recirculating and tissue-resident memory T cells. Recirculating tumor-specific memory T cells are found in the cell infiltrate of solid tumors, in the lymph and in the peripheral blood, and they constantly migrate in and out of lymph nodes, spleen, and bone marrow. Tissue-resident tumor-specific memory T cells (TRM) permanently reside in the tumor, providing local protection.Anti-PD-1/PD-L1, a type of immune checkpoint blockade (ICB) therapy, can considerably re-invigorate T cell response and lead to successful tumor control, even in patients at advanced stages. Indeed, ICB has led to unprecedented successes against many types of cancers, starting a ground-breaking revolution in tumor therapy. Unfortunately, not all patients are responsive to such treatment, thus further improvements are urgently needed. The mechanisms underlying resistance to ICB are still largely unknown. A better knowledge of the dynamics of the immune response driven by the two types of memory T cells before and after anti-PD-1/PD-L1 would provide important insights on the variability of the outcomes. This would be instrumental to design new treatments to overcome resistance.Here we provide an overview of T cell contribution to immunity against solid tumors, focusing on memory T cells. We summarize recent evidence on the involvement of recirculating memory T cells and TRM in anti-PD-1/PD-L1-elicited antitumor immunity, outline the open questions in the field, and propose that a synergic action of the two types of memory T cells is required to achieve a full response. We argue that a T-centric vision focused on the specific roles and the possible interplay between TRM and recirculating memory T cells will lead to a better understanding of anti-PD-1/PD-L1 mechanism of action, and provide new tools for improving ICB therapeutic strategy.Silvia GittoSilvia GittoAmbra NataliniFabrizio AntonangeliFrancesca Di RosaFrontiers Media S.A.articleimmune checkpoint blockadememory T cellsTRMbone marrowanti-tumor immunityImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune checkpoint blockade memory T cells TRM bone marrow anti-tumor immunity Immunologic diseases. Allergy RC581-607
spellingShingle	immune checkpoint blockade memory T cells TRM bone marrow anti-tumor immunity Immunologic diseases. Allergy RC581-607 Silvia Gitto Silvia Gitto Ambra Natalini Fabrizio Antonangeli Francesca Di Rosa The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps
description	Remarkable progress has been made in the field of anti-tumor immunity, nevertheless many questions are still open. Thus, even though memory T cells have been implicated in long-term anti-tumor protection, particularly in prevention of cancer recurrence, the bases of their variable effectiveness in tumor patients are poorly understood. Two types of memory T cells have been described according to their traffic pathways: recirculating and tissue-resident memory T cells. Recirculating tumor-specific memory T cells are found in the cell infiltrate of solid tumors, in the lymph and in the peripheral blood, and they constantly migrate in and out of lymph nodes, spleen, and bone marrow. Tissue-resident tumor-specific memory T cells (TRM) permanently reside in the tumor, providing local protection.Anti-PD-1/PD-L1, a type of immune checkpoint blockade (ICB) therapy, can considerably re-invigorate T cell response and lead to successful tumor control, even in patients at advanced stages. Indeed, ICB has led to unprecedented successes against many types of cancers, starting a ground-breaking revolution in tumor therapy. Unfortunately, not all patients are responsive to such treatment, thus further improvements are urgently needed. The mechanisms underlying resistance to ICB are still largely unknown. A better knowledge of the dynamics of the immune response driven by the two types of memory T cells before and after anti-PD-1/PD-L1 would provide important insights on the variability of the outcomes. This would be instrumental to design new treatments to overcome resistance.Here we provide an overview of T cell contribution to immunity against solid tumors, focusing on memory T cells. We summarize recent evidence on the involvement of recirculating memory T cells and TRM in anti-PD-1/PD-L1-elicited antitumor immunity, outline the open questions in the field, and propose that a synergic action of the two types of memory T cells is required to achieve a full response. We argue that a T-centric vision focused on the specific roles and the possible interplay between TRM and recirculating memory T cells will lead to a better understanding of anti-PD-1/PD-L1 mechanism of action, and provide new tools for improving ICB therapeutic strategy.
format	article
author	Silvia Gitto Silvia Gitto Ambra Natalini Fabrizio Antonangeli Francesca Di Rosa
author_facet	Silvia Gitto Silvia Gitto Ambra Natalini Fabrizio Antonangeli Francesca Di Rosa
author_sort	Silvia Gitto
title	The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps
title_short	The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps
title_full	The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps
title_fullStr	The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps
title_full_unstemmed	The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps
title_sort	emerging interplay between recirculating and tissue-resident memory t cells in cancer immunity: lessons learned from pd-1/pd-l1 blockade therapy and remaining gaps
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/38e834c142604f07a966c5b64859bc5e
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The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps

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