美国国立卫生研究院Tim F. Greten研究组的最新研究表明，肿瘤相关巨噬细胞在肝细胞癌入侵边缘引发粘膜相关不变性T（MAIT）细胞功能障碍。2023年8月17日出版的《细胞》发表了这项成果。
研究人员使用scRNA-seq、流式细胞术和与患者样本配对的共检测索引（CODEX）成像对肝细胞癌（HCC）的MAIT细胞中心进行分析。这些分析揭示了HCC中MAIT细胞的异质性和功能障碍及其浸润肝肿瘤的能力存在缺陷。研究利用机器学习工具剖析了MAIT细胞内的空间细胞相互作用网络。邻近肝脏中的共定位以及小生境CSF1R+ PD-L1+富集肿瘤相关巨噬细胞（TAM）与MAIT细胞之间的相互作用，是MAIT细胞功能障碍的关键调节要素。在使用患者样本和小鼠模型的离体共培养研究中，这种细胞-细胞相互作用扰动会重新激活MAIT细胞的细胞毒性。
这些研究表明，aPD-1/aPD-L1疗法靶向HCC患者的MAIT细胞。
据了解，MAIT细胞是人肝脏中丰富的先天样T细胞亚型。MAIT细胞在调节免疫和炎症方面起着至关重要的作用，但它们在肝癌中的作用仍然未知。
附：英文原文
Title: Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin
Author: Benjamin Ruf, Matthias Bruhns, Sepideh Babaei, Noemi Kedei, Lichun Ma, Mahler Revsine, Mohamed-Reda Benmebarek, Chi Ma, Bernd Heinrich, Varun Subramanyam, Jonathan Qi, Simon Wabitsch, Benjamin L. Green, Kylynda C. Bauer, Yuta Myojin, Layla T. Greten, Justin D. McCallen, Patrick Huang, Rajiv Trehan, Xin Wang, Amran Nur, Dana Qiang Murphy Soika, Marie Pouzolles, Christine N. Evans, Raj Chari, David E. Kleiner, William Telford, Kimia Dadkhah, Allison Ruchinskas, Merrill K. Stovroff, Jiman Kang, Kesha Oza, Mathuros Ruchirawat, Alexander Kroemer, Xin Wei Wang, Manfred Claassen, Firouzeh Korangy, Tim F. Greten
Issue&Volume: 2023/08/17
Abstract: Mucosal-associated invariant T (MAIT) cells represent an abundant innate-like T cellsubtype in the human liver. MAIT cells are assigned crucial roles in regulating immunityand inflammation, yet their role in liver cancer remains elusive. Here, we presenta MAIT cell-centered profiling of hepatocellular carcinoma (HCC) using scRNA-seq,flow cytometry, and co-detection by indexing (CODEX) imaging of paired patient samples.These analyses highlight the heterogeneity and dysfunctionality of MAIT cells in HCCand their defective capacity to infiltrate liver tumors. Machine-learning tools wereused to dissect the spatial cellular interaction network within the MAIT cell neighborhood.Co-localization in the adjacent liver and interaction between niche-occupying CSF1R+PD-L1+ tumor-associated macrophages (TAMs) and MAIT cells was identified as a key regulatoryelement of MAIT cell dysfunction. Perturbation of this cell-cell interaction in ex vivo co-culture studies using patient samples and murine models reinvigorated MAIT cellcytotoxicity. These studies suggest that aPD-1/aPD-L1 therapies target MAIT cellsin HCC patients.
DOI: 10.1016/j.cell.2023.07.026
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00804-8