Dual immune checkpoint blockade induces analogous alterations in the dysfunctional CD8+ T-cell and activated treg compartment

Author(s):
Leun, A.M. van der; Traets, J.J.H.; Vos, J.L.; Elbers, J.B.W.; Patiwael, S.; Qiao, X.H.; Machuca-Ostos, M.; Thommen, D.S.; Haanen, J.B.A.G.; Schumacher, T.N.M.; Zuur, C.L.
Published
2023
Publication type
Article / Letter to editor

Abstract

To dissect the effect of neoadjuvant PD-1 and CTLA4 blockade on intratumoral T cells in treatment-naive head and neck squamous cell carcinoma, we analyzed primary tumor immune infiltrates from responding and nonresponding patients. At baseline, a higher ratio between active (4-1BB/OX40+) and inactive regulatory CD4+ T cells was associated with immunotherapy response. Furthermore, upon therapy, this active regulatory T-cell (Treg) population showed a profound decrease in responding patients. In an analogous process, intratumoral dysfunctional CD8+ T cells displayed decreased expression of activity and dysfunction-related genes in responding patients, whereas in clinical nonresponders, natural killer cells showed an increased cytotoxic profile early upon treatment. These data reveal immunologic changes in response to dual PD-1/CTLA4 blockade, including a parallel remodeling of presumed tumor-reactive Treg and CD8+ T-cell compartments in responding patients, and indicate that the presence of activated Tregs at baseline may be associated with response.

Date issued
2023-10-05
Language
English
Is part of
Cancer Discovery (2023), Vol. 13, no. 10, p. 2212-2227
hdl
1887/4094307
doi
10.1158/2159-8290.CD-22-0851