Eschweiler, Simon, Clarke, James, Ramirez-Suastegui, Ciro, Panwar, Bharat, Madrigal, Ariel, Chee, Serena J, Karydis, Ioannis, Woo, Edwin, Alzetani, Aiman, Elsheikh, Somaia et al (show 7 more authors)
(2021)
Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy.
NATURE IMMUNOLOGY, 22 (8).
1052-+.
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<sub>FR</sub>) 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<sub>FR</sub> cells. Both T<sub>FR</sub> cell deficiency and the depletion of T<sub>FR</sub> 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CD8-Positive T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Cell Line, Tumor, Animals, Mice, Inbred C57BL, Humans, Mice, Melanoma, Disease Models, Animal, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Female, T-Lymphocytes, Regulatory, Tumor Microenvironment, CTLA-4 Antigen, Programmed Cell Death 1 Receptor, Immune Checkpoint Inhibitors, T Follicular Helper Cells |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 20 Jan 2022 09:35 |
| Last Modified: | 18 Jan 2023 21:18 |
| DOI: | 10.1038/s41590-021-00958-6 |
| Open Access URL: | https://eprints.soton.ac.uk/450396/ |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3145789 |
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