Circulating cancer-specific CD8 T cell frequency is associated with response to PD-1 blockade in Merkel cell carcinoma.

HLA-I Merkel cell carcinoma Merkel cell polyomavirus acquired resistance anti-PD-1 cancer-specific T cells nivolumab primary resistance skin cancer

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
09 Feb 2024
Historique:
received: 03 07 2023
revised: 01 12 2023
accepted: 12 01 2024
medline: 11 2 2024
pubmed: 11 2 2024
entrez: 10 2 2024
Statut: aheadofprint

Résumé

Understanding cancer immunobiology has been hampered by difficulty identifying cancer-specific T cells. Merkel cell polyomavirus (MCPyV) causes most Merkel cell carcinomas (MCCs). All patients with virus-driven MCC express MCPyV oncoproteins, facilitating identification of virus (cancer)-specific T cells. We studied MCPyV-specific T cells from 27 patients with MCC using MCPyV peptide-HLA-I multimers, 26-color flow cytometry, single-cell transcriptomics, and T cell receptor (TCR) sequencing. In a prospective clinical trial, higher circulating MCPyV-specific CD8 T cell frequency before anti-PD-1 treatment was strongly associated with 2-year recurrence-free survival (75% if detectable, 0% if undetectable, p = 0.0018; ClinicalTrial.gov: NCT02488759). Intratumorally, such T cells were typically present, but their frequency did not significantly associate with response. Circulating MCPyV-specific CD8 T cells had increased stem/memory and decreased exhaustion signatures relative to their intratumoral counterparts. These results suggest that cancer-specific CD8 T cells in the blood may play a role in anti-PD-1 responses. Thus, strategies that augment their number or mobilize them into tumors could improve outcomes.

Identifiants

DOI: 10.1016/j.xcrm.2024.101412 PMID: 38340723
pubmed: 38340723
pii: S2666-3791(24)00035-1
doi: 10.1016/j.xcrm.2024.101412
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101412

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests P.N.’s institution has received grant support from EMD Serono and Bristol Myers Squibb (BMS) as well as honoraria from Merck and EMD-Serono. D.M.K., P.N., and A.C. are co-inventors on institutionally owned patents concerning MCPyV-specific T cell receptors. K.N.S. has received honoraria/consultant fees from Adaptive Biotechnologies and research funding from BMS, AstraZeneca, and Enara Bio and holds founders’ equity in ManaT Bio, Inc. S.L.T. has received research funding from BMS and consultant fees from PathAI. D.M.P. has received research funding from BMS and Compugen; consultant fees from Amgen, BMS, Compugen, Janssen Pharmaceuticals, Normunity, RAPT Therapeutics, Regeneron, and Tizona LLC; and patent royalties through institution from BMS and owns stocks of Compugen; Mana T Bio, Inc.; RAPT Therapeutics; Tizona LCC; and TRex Bio Ltd.

Auteurs

Thomas Pulliam (T)

Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA.

Saumya Jani (S)

Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98109, USA.

Lichen Jing (L)

Department of Medicine, University of Washington, Seattle, WA 98109, USA.

Heeju Ryu (H)

Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

Ana Jojic (A)

Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

Carolyn Shasha (C)

Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

Jiajia Zhang (J)

Department of Oncology, Johns Hopkins University, Baltimore, MD 21827, USA; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA.

Rima Kulikauskas (R)

Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA.

Candice Church (C)

Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA.

Charlie Garnett-Benson (C)

Bristol Myers Squibb, Princeton, NJ 08540, USA.

Ted Gooley (T)

Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

Aude Chapuis (A)

Department of Medicine, University of Washington, Seattle, WA 98109, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

Kelly Paulson (K)

Paul G. Allen Research Center, Providence-Swedish Cancer Institute, Seattle, WA 98104, USA; Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA.

Kellie N Smith (KN)

Department of Oncology, Johns Hopkins University, Baltimore, MD 21827, USA; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA.

Drew M Pardoll (DM)

Department of Oncology, Johns Hopkins University, Baltimore, MD 21827, USA; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA.

Evan W Newell (EW)

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98109, USA; Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

David M Koelle (DM)

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA; Vaccine and Infectious Disease Department, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98109, USA; Benaroya Research Institute, Seattle, WA 98101, USA.

Suzanne L Topalian (SL)

The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.

Paul Nghiem (P)

Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98109, USA. Electronic address: pnghiem@uw.edu.

Classifications MeSH