The impact of Foxp3 + regulatory T‐cells on CD8 + T‐cell dysfunction in tumour microenvironments and responses to immune checkpoint inhibitors
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Wiley Open Access
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| Natura: | Artículo Open Access |
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Wiley
2024
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| _version_ | 1867012656075898880 |
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| author | Mikhaël Attias Ciriaco A. Piccirillo |
| author_facet | Mikhaël Attias Ciriaco A. Piccirillo Mikhaël Attias Ciriaco A. Piccirillo |
| collection | Wiley Open Access |
| contents | The impact of Foxp3 + regulatory T‐cells on CD8 + T‐cell dysfunction in tumour microenvironments and responses to immune checkpoint inhibitors Mikhaël Attias Ciriaco A. Piccirillo British Journal of Pharmacology Immune checkpoint inhibitors (ICIs) have been a breakthrough in cancer therapy, inducing durable remissions in responding patients. However, they are associated with variable outcomes, spanning from disease hyperprogression to complete responses with the onset of immune‐related adverse events. The consequences of checkpoint inhibition on Foxp3 + regulatory T (T reg ) cells remain unclear but could provide key insights into these variable outcomes. In this review, we first cover the mechanisms that underlie the development of hot and cold tumour microenvironments, which determine the efficacy of immunotherapy. We then outline how differences in tumour‐intrinsic immunogenicity, T‐cell trafficking, local metabolic environments and inhibitory checkpoint signalling differentially impair CD8 + T‐cell function in tumour microenvironments, all the while promoting T reg ‐cell suppressive activity. Finally, we focus on the mechanisms that enable the induction of polyfunctional CD8 + T‐cells upon checkpoint blockade and discuss the role of ICI‐induced T reg ‐cell reactivation in acquired resistance to treatment. LINKED ARTICLES This article is part of a themed issue Immunotherapy in Cancer. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.6/issuetoc 10.1111/bph.16313 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| doi_str_mv | 10.1111/bph.16313 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_bph_16313 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | The impact of Foxp3 + regulatory T‐cells on CD8 + T‐cell dysfunction in tumour microenvironments and responses to immune checkpoint inhibitors Mikhaël Attias Ciriaco A. Piccirillo British Journal of Pharmacology The impact of Foxp3 + regulatory T‐cells on CD8 + T‐cell dysfunction in tumour microenvironments and responses to immune checkpoint inhibitors Mikhaël Attias Ciriaco A. Piccirillo British Journal of Pharmacology Immune checkpoint inhibitors (ICIs) have been a breakthrough in cancer therapy, inducing durable remissions in responding patients. However, they are associated with variable outcomes, spanning from disease hyperprogression to complete responses with the onset of immune‐related adverse events. The consequences of checkpoint inhibition on Foxp3 + regulatory T (T reg ) cells remain unclear but could provide key insights into these variable outcomes. In this review, we first cover the mechanisms that underlie the development of hot and cold tumour microenvironments, which determine the efficacy of immunotherapy. We then outline how differences in tumour‐intrinsic immunogenicity, T‐cell trafficking, local metabolic environments and inhibitory checkpoint signalling differentially impair CD8 + T‐cell function in tumour microenvironments, all the while promoting T reg ‐cell suppressive activity. Finally, we focus on the mechanisms that enable the induction of polyfunctional CD8 + T‐cells upon checkpoint blockade and discuss the role of ICI‐induced T reg ‐cell reactivation in acquired resistance to treatment. LINKED ARTICLES This article is part of a themed issue Immunotherapy in Cancer. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.6/issuetoc 10.1111/bph.16313 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| title | The impact of Foxp3 + regulatory T‐cells on CD8 + T‐cell dysfunction in tumour microenvironments and responses to immune checkpoint inhibitors |
| topic | British Journal of Pharmacology |
| url | https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16313 |