美国国立卫生研究院Steven A. Rosenberg等研究人员合作揭示转移性癌症患者体内循环新抗原反应性CD8⁺ T细胞的表型特征。该研究于2023年11月30日在线发表于国际一流学术期刊《癌细胞》。

通过对来自6名转移性癌症患者的36个新抗原特异性T细胞克隆进行单细胞转录组分析，研究人员报告了抗肿瘤外周血（PBL）衍生CD8⁺ T细胞（NeoTCR_PBL）的转录和细胞表面特征。对肿瘤浸润淋巴细胞（TIL）和PBL-新抗原特异性T细胞进行比较后发现，NeoTCR_PBL T细胞的频率较低，与TIL对应细胞相比，NeoTCR_PBL T细胞表现出较少的功能障碍记忆表型。对100种抗肿瘤TCR克隆型的分析表明，大多数NeoTCR_PBL群体的靶标与TIL相同。然而，NeoTCR_PBL TCR反应谱仅与TIL部分共享。

对来自6名未来患者骨髓干细胞的NeoTCR_PBL特征衍生TCR的预测和测试表明，针对肿瘤突变、病毒癌基因和患者来源肿瘤的克隆型高度富集。因此，NeoTCR_PBL特征为从癌症患者的PBL中鉴定抗肿瘤T细胞提供了另一种来源，可用于免疫监测和免疫疗法。

据介绍，来自PBL的循环T细胞可以提供丰富而非侵入性的抗肿瘤T细胞来源。

附：英文原文

Title: Phenotypic signatures of circulating neoantigen-reactive CD8+ T cells in patients with metastatic cancers

Author: Rami Yossef, Sri Krishna, Sivasish Sindiri, Frank J. Lowery, Amy R. Copeland, Jared J. Gartner, Maria R. Parkhurst, Neilesh B. Parikh, Kyle J. Hitscherich, Shoshana T. Levi, Praveen D. Chatani, Nikolaos Zacharakis, Noam Levin, Nolan R. Vale, Shirley K. Nah, Aaron Dinerman, Victoria K. Hill, Satyajit Ray, Alakesh Bera, Lior Levy, Li Jia, Michael C. Kelly, Stephanie L. Goff, Paul F. Robbins, Steven A. Rosenberg

Issue&Volume: 2023-11-30

Abstract: Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasivesource for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specificT cell clones from 6 metastatic cancer patients, we report the transcriptional andcell surface signatures of antitumor PBL-derived CD8+ T cells (NeoTCRPBL). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specificT cells revealed that NeoTCRPBL T cells are low in frequency and display less-dysfunctional memory phenotypes relativeto their TIL counterparts. Analysis of 100 antitumor TCR clonotypes indicates thatmost NeoTCRPBL populations target the same neoantigens as TILs. However, NeoTCRPBL TCR repertoire is only partially shared with TIL. Prediction and testing of NeoTCRPBL signature-derived TCRs from PBL of 6 prospective patients demonstrate high enrichmentof clonotypes targeting tumor mutations, a viral oncogene, and patient-derived tumor.Thus, the NeoTCRPBL signature provides an alternative source for identifying antitumor T cells from PBLof cancer patients, enabling immune monitoring and immunotherapies.

DOI: 10.1016/j.ccell.2023.11.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00396-3