Veatch et al. investigated CD4+ T cell phenotypes and functions in human melanoma. Using scRNAseq and TCR sequencing, 350 neoantigen- and tumor antigen-specific CD4+ T cells, obtained from primary tumors of four patients with melanoma, were found to express CXCL13 and PD-1, and could be subdivided into distinct functional clusters: a proliferative cluster, a Tfh-like subset colocalizing with B cells in the TME, and a cytolytic subset expressing Tim3 and IFNγ. The presence of CXCL13+ CD4+ T cells correlated with overall survival and local macrophage, CD8+ T, and B cell activation, suggesting CD4+ T cells have key and diverse beneficial roles in the TME.
Contributed by Katherine Turner
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.
Author Info: (1) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: jveatch@fredhutch.org. (2) Department of Medical Oncology, Univer
Author Info: (1) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: jveatch@fredhutch.org. (2) Department of Medical Oncology, University of Washington, Seattle, WA, USA. (3) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (4) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (5) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (6) Department of Dermatology, University of Washington, Seattle, WA, USA. (7) Department of Surgery, University of Washington, Seattle, WA, USA. (8) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (9) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (10) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (11) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (12) Department of Medical Oncology, University of Washington, Seattle, WA, USA. (13) Department of Medical Oncology, University of Washington, Seattle, WA, USA. (14) Department of Medical Oncology, University of Washington, Seattle, WA, USA. (15) Department of Surgery, University of Washington, Seattle, WA, USA. (16) Department of Medical Oncology, University of Washington, Seattle, WA, USA. (17) Department of Surgery, University of Washington, Seattle, WA, USA. (18) Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA. (19) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (20) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (21) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (22) Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
