小柯机器人

美国李莫菲特癌症研究中心Jose R. Conejo-Garcia研究揭示，卵巢癌免疫原性受一小部分祖组织驻留记忆 T 细胞亚群的控制。相关论文发表在2022年4月14日出版的《癌细胞》杂志上。

他们报告说，卵巢癌浸润性 T 细胞中肿瘤识别的标志主要局限于组织驻留记忆 (TRM) 细胞。83,454 个 CD3+CD8+CD103+CD69+ TRM 细胞的单细胞 RNA/TCR/ATAC 测序和 122 种高级别浆液性卵巢癌的免疫组织化学显示，只有祖 (TCF1low) 组织驻留 T 细胞 (TRMstem 细胞)，但不循环TCF1+ T 细胞，预测卵巢癌结果。TRM 干细胞源自过渡循环 T 细胞，这依赖于抗原亲和力/持久性，导致最终耗尽的寡克隆、食细胞、效应淋巴细胞。因此，卵巢癌确实是一种免疫原性疾病，但这取决于约 13% 的 CD8+ 肿瘤浸润性 T 细胞（约 3% 的 CD8+ 克隆型），这些细胞针对高亲和力抗原启动并维持效应 TRM 样细胞波动。

他们的结果定义了人类卵巢癌中相关肿瘤反应性 T 细胞的特征，这可能适用于其他具有不理想突变负担的肿瘤。

据介绍，尽管 T 细胞浸润和结果之间存在重复关联，但人类卵巢癌仍然对免疫治疗的反应不良。

附：英文原文

Title: Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells

Author: Carmen M. Anadon, Xiaoqing Yu, Kay Hnggi, Subir Biswas, Ricardo A. Chaurio, Alexandra Martin, Kyle K. Payne, Gunjan Mandal, Patrick Innamarato, Carly M. Harro, Jessica A. Mine, Kimberly B. Sprenger, Carla Cortina, John J. Powers, Tara Lee Costich, Bradford A. Perez, Chandler D. Gatenbee, Sandhya Prabhakaran, Douglas Marchion, Mirjam H.M. Heemskerk, Tyler J. Curiel, Alexander R. Anderson, Robert M. Wenham, Paulo C. Rodriguez, Jose R. Conejo-Garcia

Issue&Volume: 2022-04-14

Abstract: Despite repeated associations between T cell infiltration and outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that the hallmarks of tumor recognition in ovarian cancer-infiltrating T cells are primarily restricted to tissue-resident memory (TRM) cells. Single-cell RNA/TCR/ATAC sequencing of 83,454 CD3+CD8+CD103+CD69+ TRM cells and immunohistochemistry of 122 high-grade serous ovarian cancers shows that only progenitor (TCF1low) tissue-resident T cells (TRMstem cells), but not recirculating TCF1+ T cells, predict ovarian cancer outcome. TRMstem cells arise from transitional recirculating T cells, which depends on antigen affinity/persistence, resulting in oligoclonal, trogocytic, effector lymphocytes that eventually become exhausted. Therefore, ovarian cancer is indeed an immunogenic disease, but that depends on ～13% of CD8+ tumor-infiltrating T cells (～3% of CD8+ clonotypes), which are primed against high-affinity antigens and maintain waves of effector TRM-like cells. Our results define the signature of relevant tumor-reactive T cells in human ovarian cancer, which could be applicable to other tumors with unideal mutational burden.

DOI: 10.1016/j.ccell.2022.03.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00123-4

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