小柯机器人

美国伊利诺伊大学Ekrem Emrah Er、斯隆凯特琳癌症研究所Morgan Huse等研究人员合作发现，细胞毒性淋巴细胞可在肿瘤中靶向生物物理特征。相关论文于2021年3月22日在线发表在《免疫》杂志上。

研究人员发现，促进迁移和转移性侵袭的心肌相关转录因子（MRTF）使得癌细胞对免疫系统敏感。在转移小鼠模型中，具有高MRTF表达的黑素瘤和乳腺癌细胞被细胞毒性淋巴细胞选择性清除。通过使用免疫检查点封锁（ICB）抗体进行治疗，可以进一步增强这种免疫监视表型。研究人员还观察到人类黑素瘤中的高MRTF信号与患者的ICB疗效相关。

使用生物物理和功能分析，研究人员表明MRTF过表达使丝状肌动蛋白的细胞骨架僵化，这种机械变化使小鼠和人类癌细胞更容易受到细胞毒性T淋巴细胞和自然杀伤细胞的攻击。

总的来说，这些结果表明免疫监视具有机械功能，被称为机械监视，这与靶向转移性疾病特别相关。 

据了解，免疫细胞通过识别指示致癌性转化的细胞特征来鉴定和破坏肿瘤。

附：英文原文

Title: Cytotoxic lymphocytes target characteristic biophysical vulnerabilities in cancer

Author: Maria Tello-Lafoz, Katja Srpan, Elisa E. Sanchez, Jing Hu, Jan Remsik, Yevgeniy Romin, Annalisa Calò, Douglas Hoen, Umeshkumar Bhanot, Luc Morris, Adrienne Boire, Katharine C. Hsu, Joan Massagué, Morgan Huse, Ekrem Emrah Er

Issue&Volume: 2021-03-22

Abstract: Immune cells identify and destroy tumors by recognizing cellular traits indicativeof oncogenic transformation. In this study, we found that myocardin-related transcriptionfactors (MRTFs), which promote migration and metastatic invasion, also sensitize cancercells to the immune system. Melanoma and breast cancer cells with high MRTF expressionwere selectively eliminated by cytotoxic lymphocytes in mouse models of metastasis.This immunosurveillance phenotype was further enhanced by treatment with immune checkpointblockade (ICB) antibodies. We also observed that high MRTF signaling in human melanomais associated with ICB efficacy in patients. Using biophysical and functional assays,we showed that MRTF overexpression rigidified the filamentous actin cytoskeleton andthat this mechanical change rendered mouse and human cancer cells more vulnerableto cytotoxic T lymphocytes and natural killer cells. Collectively, these results suggestthat immunosurveillance has a mechanical dimension, which we call mechanosurveillance,that is particularly relevant for the targeting of metastatic disease.

DOI: 10.1016/j.immuni.2021.02.020

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00086-8

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