小柯机器人

近日，美国哈佛医学院Kai W. Wucherpfennig等研究人员合作发现，组织驻留记忆和循环T细胞是手术前癌症免疫疗法的早期反应者。这一研究成果于2022年7月7日在线发表在国际学术期刊《细胞》上。

研究人员在一项临床试验（NCT02919683）中，对接受新辅助抗PD-1或抗PD-1/CTLA-4治疗的口腔癌患者的肿瘤浸润和循环免疫细胞早期动力学进行了表征。肿瘤浸润的CD8 T细胞在免疫治疗过程中克隆性扩增，并表达了升高的组织驻留记忆和细胞毒性程序，这些程序在治疗前已经活跃，支持快速反应的能力。

系统性的靶标发现显示，治疗后扩增的肿瘤T细胞克隆能识别几种自我抗原，包括癌症特异性抗原MAGEA1。治疗还诱发了全身性的免疫反应，其特点是富含肿瘤浸润性T细胞克隆型的活化T细胞的扩增，包括治疗前未检测到的原有和新出现的克隆型。激活的血液CD8 T细胞，特别是治疗前PD-1阳性的KLRG1阴性T细胞的频率，与肿瘤内的病理反应密切相关。这些结果证明了新辅助检查点阻断如何诱导局部和全身的肿瘤免疫力。

据了解，新辅助免疫检查点阻断治疗已显示出有希望的临床活性。

附：英文原文

Title: Tissue-resident memory and circulating T cells are early responders to pre-surgical cancer immunotherapy

Author: Adrienne M. Luoma, Shengbao Suo, Yifan Wang, Lauren Gunasti, Caroline B.M. Porter, Nancy Nabilsi, Jenny Tadros, Andrew P. Ferretti, Sida Liao, Cagan Gurer, Yu-Hui Chen, Shana Criscitiello, Cora A. Ricker, Danielle Dionne, Orit Rozenblatt-Rosen, Ravindra Uppaluri, Robert I. Haddad, Orr Ashenberg, Aviv Regev, Eliezer M. Van Allen, Gavin MacBeath, Jonathan D. Schoenfeld, Kai W. Wucherpfennig

Issue&Volume: 2022-07-07

Abstract: Neoadjuvant immune checkpoint blockade has shown promising clinical activity. Here,we characterized early kinetics in tumor-infiltrating and circulating immune cellsin oral cancer patients treated with neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 ina clinical trial (NCT02919683). Tumor-infiltrating CD8 T cells that clonally expandedduring immunotherapy expressed elevated tissue-resident memory and cytotoxicity programs,which were already active prior to therapy, supporting the capacity for rapid response.Systematic target discovery revealed that treatment-expanded tumor T cell clones inresponding patients recognized several self-antigens, including the cancer-specificantigen MAGEA1. Treatment also induced a systemic immune response characterized byexpansion of activated T cells enriched for tumor-infiltrating T cell clonotypes,including both pre-existing and emergent clonotypes undetectable prior to therapy.The frequency of activated blood CD8 T cells, notably pre-treatment PD-1-positiveKLRG1-negative T cells, was strongly associated with intra-tumoral pathological response.These results demonstrate how neoadjuvant checkpoint blockade induces local and systemictumor immunity.

DOI: 10.1016/j.cell.2022.06.018

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00723-1