Title
Neoantigen-specific CD4 + T cells in human melanoma have diverse differentiation states and correlate with CD8 + T cell, macrophage, and B cell function
Document Type
Article
Publication Date
4-11-2022
Publication Title
Cancer cell
Keywords
oregon; portland; chiles; Animals; Antigens, Neoplasm; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Humans; Macrophages; Melanoma; Mice; Tumor Microenvironment
Abstract
CD4+ T cells that recognize tumor antigens are required for immune checkpoint inhibitor efficacy in murine models, but their contributions in human cancer are unclear. We used single-cell RNA sequencing and T cell receptor sequences to identify signatures and functional correlates of tumor-specific CD4+ T cells infiltrating human melanoma. Conventional CD4+ T cells that recognize tumor neoantigens express CXCL13 and are subdivided into clusters expressing memory and T follicular helper markers, and those expressing cytolytic markers, inhibitory receptors, and IFN-γ. The frequency of CXCL13+ CD4+ T cells in the tumor correlated with the transcriptional states of CD8+ T cells and macrophages, maturation of B cells, and patient survival. Similar correlations were observed in a breast cancer cohort. These results identify phenotypes and functional correlates of tumor-specific CD4+ T cells in melanoma and suggest the possibility of using such cells to modify the tumor microenvironment.
Clinical Institute
Cancer
Department
Earle A. Chiles Research Institute
Department
Oncology
Recommended Citation
Veatch, Joshua R; Lee, Sylvia M; Shasha, Carolyn; Singhi, Naina; Szeto, Julia L; Moshiri, Ata S; Kim, Teresa S; Smythe, Kimberly; Kong, Paul; Fitzgibbon, Matthew; Jesernig, Brenda; Bhatia, Shailender; Tykodi, Scott S; Hall, Evan T; Byrd, David R; Thompson, John A; Pillarisetty, Venu G; Duhen, Thomas; McGarry Houghton, A; Newell, Evan; Gottardo, Raphael; and Riddell, Stanley R, "Neoantigen-specific CD4 + T cells in human melanoma have diverse differentiation states and correlate with CD8 + T cell, macrophage, and B cell function" (2022). Articles, Abstracts, and Reports. 6000.
https://digitalcommons.providence.org/publications/6000