PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy.
Details
Serval ID
serval:BIB_61FA7BC39A7C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy.
Journal
Journal for immunotherapy of cancer
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Publication state
Published
Issued date
11/2020
Peer-reviewed
Oui
Volume
8
Number
2
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Clinical benefit from programmed cell death 1 receptor (PD-1) inhibitors relies on reinvigoration of endogenous antitumor immunity. Nonetheless, robust immunological markers, based on circulating immune cell subsets associated with therapeutic efficacy are yet to be validated.
We isolated peripheral blood mononuclear cell from three independent cohorts of melanoma and Merkel cell carcinoma patients treated with PD-1 inhibitor, at baseline and longitudinally after therapy. Using multiparameter flow cytometry and cell sorting, we isolated four subsets of CD8 <sup>+</sup> T cells, based on PD-1 and TIGIT expression profiles. We performed phenotypic characterization, T cell receptor sequencing, targeted transcriptomic analysis and antitumor reactivity assays to thoroughly characterize each of these subsets.
We documented that the frequency of circulating PD-1 <sup>+</sup> TIGIT <sup>+</sup> (DPOS) CD8 <sup>+</sup> T-cells after 1 month of anti-PD-1 therapy was associated with clinical response and overall survival. This DPOS T-cell population was enriched in highly activated T-cells, tumor-specific and emerging T-cell clonotypes and T lymphocytes overexpressing CXCR5, a key marker of the CD8 cytotoxic follicular T cell population. Additionally, transcriptomic profiling defined a specific gene signature for this population as well as the overexpression of specific pathways associated with the therapeutic response.
Our results provide a convincing rationale for monitoring this PD-1 <sup>+</sup> TIGIT <sup>+</sup> circulating population as an early cellular-based marker of therapeutic response to anti-PD-1 therapy.
We isolated peripheral blood mononuclear cell from three independent cohorts of melanoma and Merkel cell carcinoma patients treated with PD-1 inhibitor, at baseline and longitudinally after therapy. Using multiparameter flow cytometry and cell sorting, we isolated four subsets of CD8 <sup>+</sup> T cells, based on PD-1 and TIGIT expression profiles. We performed phenotypic characterization, T cell receptor sequencing, targeted transcriptomic analysis and antitumor reactivity assays to thoroughly characterize each of these subsets.
We documented that the frequency of circulating PD-1 <sup>+</sup> TIGIT <sup>+</sup> (DPOS) CD8 <sup>+</sup> T-cells after 1 month of anti-PD-1 therapy was associated with clinical response and overall survival. This DPOS T-cell population was enriched in highly activated T-cells, tumor-specific and emerging T-cell clonotypes and T lymphocytes overexpressing CXCR5, a key marker of the CD8 cytotoxic follicular T cell population. Additionally, transcriptomic profiling defined a specific gene signature for this population as well as the overexpression of specific pathways associated with the therapeutic response.
Our results provide a convincing rationale for monitoring this PD-1 <sup>+</sup> TIGIT <sup>+</sup> circulating population as an early cellular-based marker of therapeutic response to anti-PD-1 therapy.
Keywords
CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Carcinoma, Merkel Cell/blood, Carcinoma, Merkel Cell/drug therapy, Carcinoma, Merkel Cell/immunology, Humans, Immune Checkpoint Inhibitors/pharmacology, Melanoma/blood, Melanoma/drug therapy, Melanoma/immunology, Predictive Value of Tests, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Programmed Cell Death 1 Receptor/biosynthesis, Programmed Cell Death 1 Receptor/blood, Programmed Cell Death 1 Receptor/immunology, Receptors, CXCR5/immunology, Receptors, Immunologic/biosynthesis, Receptors, Immunologic/blood, Receptors, Immunologic/immunology, T-Lymphocyte Subsets/immunology, CD8-Positive T-Lymphocytes, costimulatory and inhibitory T-Cell receptors, immunotherapy, melanoma, programmed cell death 1 receptor
Pubmed
Web of science
Open Access
Yes
Create date
28/02/2022 12:45
Last modification date
23/03/2024 8:24