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Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy.
- Source :
-
Nature immunology [Nat Immunol] 2021 Aug; Vol. 22 (8), pp. 1052-1063. Date of Electronic Publication: 2021 Jun 24. - Publication Year :
- 2021
-
Abstract
- Immune-checkpoint blockade (ICB) has shown remarkable clinical success in boosting antitumor immunity. However, the breadth of its cellular targets and specific mode of action remain elusive. We find that tumor-infiltrating follicular regulatory T (T <subscript>FR</subscript> ) cells are prevalent in tumor tissues of several cancer types. They are primarily located within tertiary lymphoid structures and exhibit superior suppressive capacity and in vivo persistence as compared with regulatory T cells, with which they share a clonal and developmental relationship. In syngeneic tumor models, anti-PD-1 treatment increases the number of tumor-infiltrating T <subscript>FR</subscript> cells. Both T <subscript>FR</subscript> cell deficiency and the depletion of T <subscript>FR</subscript> cells with anti-CTLA-4 before anti-PD-1 treatment improve tumor control in mice. Notably, in a cohort of 271 patients with melanoma, treatment with anti-CTLA-4 followed by anti-PD-1 at progression was associated with better a survival outcome than monotherapy with anti-PD-1 or anti-CTLA-4, anti-PD-1 followed by anti-CTLA-4 at progression or concomitant combination therapy.<br /> (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Subjects :
- Animals
Antineoplastic Agents therapeutic use
Antineoplastic Combined Chemotherapy Protocols therapeutic use
CD8-Positive T-Lymphocytes immunology
Cell Line, Tumor
Disease Models, Animal
Female
Humans
Mice
Mice, Inbred C57BL
T Follicular Helper Cells immunology
Tumor Microenvironment immunology
CTLA-4 Antigen antagonists & inhibitors
Immune Checkpoint Inhibitors therapeutic use
Lymphocytes, Tumor-Infiltrating immunology
Melanoma drug therapy
Programmed Cell Death 1 Receptor antagonists & inhibitors
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 22
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34168370
- Full Text :
- https://doi.org/10.1038/s41590-021-00958-6