美国Fred Hutchinson癌症研究中心Joshua R. Veatch等研究人员发现，人类黑色素瘤中的新抗原特异性CD4⁺ T细胞具有不同的分化状态，并与CD8⁺ T细胞、巨噬细胞和B细胞功能相关联。2022年4月11日出版的《癌细胞》杂志发表了这项成果。

研究人员使用单细胞RNA测序和T细胞受体序列，来识别渗入人类黑色素瘤的肿瘤特异性CD4⁺ T细胞的特征和功能相关性。识别肿瘤新抗原的常规CD4⁺ T细胞表达CXCL13，并被细分为表达记忆和T滤泡辅助标记的亚群，以及表达细胞溶解标记、抑制性受体和IFN-γ的亚群。肿瘤中CXCL13⁺CD4⁺ T细胞的频率与CD8⁺ T细胞和巨噬细胞的转录状态、B细胞的成熟度和病人的生存率相关。在一个乳腺癌队列中也观察到类似的相关性。这些结果确定了黑色素瘤中肿瘤特异性CD4⁺ T细胞的表型和功能相关性，并提出了使用这种细胞来改变肿瘤微环境的可能性。

据介绍，在小鼠模型中，识别肿瘤抗原的CD4⁺ T细胞是免疫检查点抑制剂疗效的必要条件，但它们在人类癌症中的贡献尚不清楚。

附：英文原文

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

Author: Joshua R. Veatch, Sylvia M. Lee, Carolyn Shasha, Naina Singhi, Julia L. Szeto, Ata S. Moshiri, Teresa S. Kim, Kimberly Smythe, Paul Kong, Matthew Fitzgibbon, Brenda Jesernig, Shailender Bhatia, Scott S. Tykodi, Evan T. Hall, David R. Byrd, John A. Thompson, Venu G. Pillarisetty, Thomas Duhen, A. McGarry Houghton, Evan Newell, Raphael Gottardo, Stanley R. Riddell

Issue&Volume: 2022/04/11

Abstract: CD4+ T cells that recognize tumor antigens are required for immune checkpoint inhibitorefficacy in murine models, but their contributions in human cancer are unclear. Weused single-cell RNA sequencing and T cell receptor sequences to identify signaturesand 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 frequencyof 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 correlationswere observed in a breast cancer cohort. These results identify phenotypes and functionalcorrelates of tumor-specific CD4+ T cells in melanoma and suggest the possibility of using such cells to modify thetumor microenvironment.

DOI: 10.1016/j.ccell.2022.03.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00121-0