American Association for Cancer Research
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Supplementary Figure S12 from Single-cell Profiles and Prognostic Impact of Tumor-Infiltrating Lymphocytes Coexpressing CD39, CD103, and PD-1 in Ovarian Cancer

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journal contribution
posted on 2023-03-31, 22:45 authored by Céline M. Laumont, Maartje C.A. Wouters, Julian Smazynski, Nicole S. Gierc, Elizabeth A. Chavez, Lauren C. Chong, Shelby Thornton, Katy Milne, John R. Webb, Christian Steidl, Brad H. Nelson

Supplementary Figure S12 shows the expression level of genes associated with tissue-resident memory CD8+ T cells across triple-positive, 'other' and triple-negative CD8+ T cell subsets.

Funding

BC Cancer Foundation

Canadian Cancer Society

Canadian Institutes of Health Research

Terry Fox Research Institute

Cancer Research Society

Canada's Networks of Centres of Excellence

Paul G. Allen Frontiers Group

CIHR

Michael Smith Foundation for Health Research

MSFHR

History

ARTICLE ABSTRACT

Tumor-infiltrating lymphocytes (TIL) are strongly associated with survival in most cancers; however, the tumor-reactive subset that drives this prognostic effect remains poorly defined. CD39, CD103, and PD-1 have been independently proposed as markers of tumor-reactive CD8+ TIL in various cancers. We evaluated the phenotype, clonality, and prognostic significance of TIL expressing various combinations of these markers in high-grade serous ovarian cancer (HGSC), a malignancy in need of more effective immunotherapeutic approaches. Expression of CD39, CD103, PD-1, and other immune markers was assessed by high-dimensional flow cytometry, single-cell sequencing, and multiplex immunofluorescence of primary and matched pre/post-chemotherapy HGSC specimens. Coexpression of CD39, CD103, and PD-1 (“triple-positive” phenotype) demarcated subsets of CD8+ TIL and CD4+ regulatory T cells (Treg) with a highly activated/exhausted phenotype. Triple-positive CD8+ TIL exhibited reduced T-cell receptor (TCR) diversity and expressed genes involved in both cytolytic and humoral immunity. Triple-positive Tregs exhibited higher TCR diversity and a tumor-resident phenotype. Triple-positive TIL showed superior prognostic impact relative to TIL expressing other combinations of these markers. TIGIT was uniquely upregulated on triple-positive CD8+ effector cells relative to their CD4+ Treg counterparts. Coexpression of CD39, CD103, and PD-1 demarcates highly activated CD8+ and CD4+ TIL with inferred roles in cytolytic, humoral, and regulatory immune functions. Triple-positive TIL demonstrate exceptional prognostic significance and express compelling targets for combination immunotherapy, including PD-1, CD39, and TIGIT.