Merkel cell polyomavirus-specific and CD39+CLA+CD8 T cells as blood-based predictive biomarkers for PD-1 blockade in Merkel cell carcinoma

被引：12

作者：

Ryu, Heeju ^{[1
]}

Bi, Timothy M. ^{[1
]}

Pulliam, Thomas H. ^{[2
]}

Sarkar, Korok ^{[1
]}

Church, Candice D. ^{[2
]}

Kumar, Nandita ^{[1
,3
]}

Mayer-Blackwell, Koshlan ^{[1
]}

Jani, Saumya ^{[2
,3
]}

Ramchurren, Nirasha ^{[4
]}

Hansen, Ulla K. ^{[5
]}

Hadrup, Sine R. ^{[5
]}

Fling, Steven P. ^{[4
]}

Koelle, David M. ^{[1
,3
,6
,7
,8
]}

Nghiem, Paul ^{[2
]}

Newell, Evan W. ^{[1
,3
]}

机构：

[1] Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

[2] Univ Washington, Dept Med, Div Dermatol, Seattle, WA USA

[3] Univ Washington, Dept Lab Med & Pathol, Seattle, WA 98195 USA

[4] Fred Hutchinson Canc Ctr, Canc Immunotherapy Trails Network, Seattle, WA USA

[5] Tech Univ Denmark, Dept Hlth Technol, Lyngby, Denmark

[6] Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA USA

[7] Univ Washington, Dept Global Hlth, Seattle, WA USA

[8] Benaroya Res Inst, Seattle, WA USA

来源：

CELL REPORTS MEDICINE | 2024年 / 5卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

CD8(+); EXPRESSION; RESPONSES; ANTIGEN; ANTIBODIES; CYTOMETRY; SURVIVAL; FEATURES; DIVERSE; TISSUES;

D O I：

10.1016/j.xcrm.2023.101390

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Merkel cell carcinoma is a skin cancer often driven by Merkel cell polyomavirus (MCPyV) with high rates of response to anti -PD -1 therapy despite low mutational burden. MCPyV-specific CD8 T cells are implicated in anti -PD -1 -associated immune responses and provide a means to directly study tumor -specific T cell responses to treatment. Using mass cytometry and combinatorial tetramer staining, we find that baseline frequencies of blood MCPyV-specific cells correlated with response and survival. Frequencies of these cells decrease markedly during response to therapy. Phenotypes of MCPyV-specific CD8 T cells have distinct expression patterns of CD39, cutaneous lymphocyte -associated antigen (CLA), and CD103. Correspondingly, overall bulk CD39+CLA+ CD8 T cell frequencies in blood correlate with MCPyV-specific cell frequencies and similarly predicted favorable clinical outcomes. Conversely, frequencies of CD39+CD103+ CD8 T cells are associated with tumor burden and worse outcomes. These cell subsets can be useful as biomarkers and to isolate blood -derived tumor -specific T cells.

引用

页数：20

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