利用人类结直肠癌（CRC）样本和小鼠CRC模型，研究人员发现恶性肿瘤前期或非肿瘤性结肠中的大多数γδT细胞表现出细胞毒性标记，而肿瘤浸润的γδT细胞则表现出致瘤性特征。这些截然不同的T细胞特征与人类和小鼠中不同的T细胞受体（TCR）-Vγδ基因的使用有关。纵向交叉遗传学和抗体依赖策略靶向稳定状态下富集在上皮细胞中的小鼠γδ T细胞，这导致了肿瘤的高度发展，而靶向CRC期间积累的γδ亚群则导致了肿瘤的减少。这些结果揭示了γδ T细胞亚群在时间上的促肿瘤和抗肿瘤作用。
据介绍，γδT细胞在平衡状态下代表了肠道淋巴细胞的很大一部分，但它们也构成了渗入CRC的主要淋巴细胞群。然而，它们对CRC发展或进展的时间贡献仍然不清楚。
附：英文原文
Title: TCR-Vγδ usage distinguishes protumor from antitumor intestinal γδ T cell subsets
Author: Bernardo S. Reis, Patrick W. Darcy, Iasha Z. Khan, Christine S. Moon, Adam E. Kornberg, Vanessa S. Schneider, Yelina Alvarez, Olawale Eleso, Caixia Zhu, Marina Schernthanner, Ainsley Lockhart, Aubrey Reed, Juliana Bortolatto, Tiago B. R. Castro, Angelina M. Bilate, Sergei Grivennikov, Arnold S. Han, Daniel Mucida
Issue&Volume: 2022-07-15
Abstract: γδ T cells represent a substantial fraction of intestinal lymphocytes at homeostasis, but they also constitute a major lymphocyte population infiltrating colorectal cancers (CRCs); however, their temporal contribution to CRC development or progression remains unclear. Using human CRC samples and murine CRC models, we found that most γδ T cells in premalignant or nontumor colons exhibit cytotoxic markers, whereas tumor-infiltrating γδ T cells express a protumorigenic profile. These contrasting T cell profiles were associated with distinct T cell receptor (TCR)–Vγδ gene usage in both humans and mice. Longitudinal intersectional genetics and antibody-dependent strategies targeting murine γδ T cells enriched in the epithelium at steady state led to heightened tumor development, whereas targeting γδ subsets that accumulate during CRC resulted in reduced tumor growth. Our results uncover temporal pro- and antitumor roles for γδ T cell subsets.
DOI: abj8695
Source: https://www.science.org/doi/10.1126/science.abj8695