小柯机器人

美国加州大学Matthew F. Krummel小组取得一项新突破。他们揭示了肿瘤巨噬细胞和耗竭CD8⁺ T细胞之间的时空相关性。相关论文于2022年5月26日发表在《癌细胞》杂志上。

研究人员发现肿瘤微环境(TME)中肿瘤相关巨噬细胞(TAM)和耗尽的T细胞 (Tex)生物学之间存在广泛的联系。研究证明，体内TAM降低减少了肿瘤浸润 CD8⁺ T细胞的耗竭基序，揭示出它们的效应潜力。反过来，转录和表观遗传分析表明，Tex表达因子会主动将单核细胞招募到TME并调控其分化。使用晶格光片显微镜，研究发现TAM和CD8⁺ T细胞参与独特、持久、抗原特异性突触相互作用，这些相互作用不能激活T细胞，但会使它们活力减弱，并且这种作用在缺氧条件下会加速。空间分辨测序支持时空自执行正反馈通路，该通路发挥保护而非破坏肿瘤的作用。

据悉，T细胞耗竭是抗肿瘤免疫的主要障碍。然而，TME中其他免疫细胞如何促成这种功能失调仍然未知。

附：英文原文

Title: Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells in cancer

Author: Kelly Kersten, Kenneth H. Hu, Alexis J. Combes, Bushra Samad, Tory Harwin, Arja Ray, Arjun Arkal Rao, En Cai, Kyle Marchuk, Jordan Artichoker, Tristan Courau, Quanming Shi, Julia Belk, Ansuman T. Satpathy, Matthew F. Krummel

Issue&Volume: 2022-05-26

Abstract: T cell exhaustion is a major impediment to antitumor immunity. However, it remainselusive how other immune cells in the tumor microenvironment (TME) contribute to thisdysfunctional state. Here, we show that the biology of tumor-associated macrophages(TAMs) and exhausted T cells (Tex) in the TME is extensively linked. We demonstrate that in vivo depletion of TAMs reduces exhaustion programs in tumor-infiltrating CD8+ T cells and reinvigorates their effector potential. Reciprocally, transcriptionaland epigenetic profiling reveals that Tex express factors that actively recruit monocytes to the TME and shape their differentiation.Using lattice light sheet microscopy, we show that TAM and CD8+ T cells engage in unique, long-lasting, antigen-specific synaptic interactions thatfail to activate T cells but prime them for exhaustion, which is then acceleratedin hypoxic conditions. Spatially resolved sequencing supports a spatiotemporal self-enforcingpositive feedback circuit that is aligned to protect rather than destroy a tumor.

DOI: 10.1016/j.ccell.2022.05.004

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00215-X

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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