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Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy

Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy
Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy
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 (TFR) 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 TFR cells. Both TFR cell deficiency and the depletion of TFR 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.
1529-2908
1052-1063
Eschweiler, Simon
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Clarke, James
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Ramírez-suástegui, Ciro
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Panwar, Bharat
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Madrigal, Ariel
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Chee, Serena J.
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Karydis, Ioannis
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Woo, Edwin
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Alzetani, Aiman
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Elsheikh, Somaia
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Hanley, C. J.
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Thomas, G. J.
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Friedmann, Peter S.
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Sanchez-elsner, Tilman
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Ay, Ferhat
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Ottensmeier, Christian H.
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Vijayanand, Pandurangan
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Eschweiler, Simon
66facd8e-da6c-4455-acee-a3a475342dca
Clarke, James
c6d96a48-29b7-4ed2-85b0-cdd4a41139b3
Ramírez-suástegui, Ciro
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Panwar, Bharat
7e9a1363-0a88-4e57-aaab-5ac67cd05353
Madrigal, Ariel
a9e9a737-f068-4040-aff8-1b9b1763adf1
Chee, Serena J.
51a261fc-2b72-43cc-98dd-79617de7573b
Karydis, Ioannis
95a2388c-7165-40e1-8b73-87234caea36d
Woo, Edwin
3bd695f0-4657-4f49-a07e-2576011f19a2
Alzetani, Aiman
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Elsheikh, Somaia
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Hanley, C. J.
44c46dcb-d239-4d41-9fc5-ca7c2efad6cc
Thomas, G. J.
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Friedmann, Peter S.
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Sanchez-elsner, Tilman
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Ay, Ferhat
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Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1

Eschweiler, Simon, Clarke, James, Ramírez-suástegui, Ciro, Panwar, Bharat, Madrigal, Ariel, Chee, Serena J., Karydis, Ioannis, Woo, Edwin, Alzetani, Aiman, Elsheikh, Somaia, Hanley, C. J., Thomas, G. J., Friedmann, Peter S., Sanchez-elsner, Tilman, Ay, Ferhat, Ottensmeier, Christian H. and Vijayanand, Pandurangan (2021) Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy. Nature Immunology, 22 (8), 1052-1063. (doi:10.1038/s41590-021-00958-6).

Record type: Article

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 (TFR) 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 TFR cells. Both TFR cell deficiency and the depletion of TFR 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.

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Eschweiler et al., 2021 - accepted - Accepted Manuscript
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Eschweiler et al., 2021 - Version of Record
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More information

Accepted/In Press date: 12 May 2021
e-pub ahead of print date: 24 June 2021
Published date: 1 August 2021

Identifiers

Local EPrints ID: 450396
URI: http://eprints.soton.ac.uk/id/eprint/450396
ISSN: 1529-2908
PURE UUID: 3a05791e-55eb-4594-9300-656404a52124
ORCID for Tilman Sanchez-elsner: ORCID iD orcid.org/0000-0003-1915-2410

Catalogue record

Date deposited: 27 Jul 2021 17:23
Last modified: 26 Nov 2021 02:52

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Contributors

Author: Simon Eschweiler
Author: James Clarke
Author: Ciro Ramírez-suástegui
Author: Bharat Panwar
Author: Ariel Madrigal
Author: Serena J. Chee
Author: Ioannis Karydis
Author: Edwin Woo
Author: Aiman Alzetani
Author: Somaia Elsheikh
Author: C. J. Hanley
Author: G. J. Thomas
Author: Peter S. Friedmann
Author: Ferhat Ay
Author: Pandurangan Vijayanand

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