Neoantigen-specific CD4+ T cells in human melanoma have diverse differentiation states and correlate with CD8+ T cell, macrophage, and B cell function

应用领域

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.

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基因水平：PCR Array、RT-PCR、PCR、单细胞测序
蛋白水平：MSD、Luminex、CBA、Elispot、Antibody Array、ELISA、Sengenics
细胞水平：细胞染色、细胞分选、细胞培养、细胞功能
组织水平：空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析：流式数据分析、组化数据分析、多因子数据分析

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