Cytotoxic lymphocytes target characteristic biophysical vulnerabilities in cancer Journal Article


Authors: Tello-Lafoz, M.; Srpan, K.; Sanchez, E. E.; Hu, J.; Remsik, J.; Romin, Y.; Calò, A.; Hoen, D.; Bhanot, U.; Morris, L.; Boire, A.; Hsu, K. C.; Massagué, J.; Huse, M.; Er, E. E.
Article Title: Cytotoxic lymphocytes target characteristic biophysical vulnerabilities in cancer
Abstract: Immune cells identify and destroy tumors by recognizing cellular traits indicative of oncogenic transformation. In this study, we found that myocardin-related transcription factors (MRTFs), which promote migration and metastatic invasion, also sensitize cancer cells to the immune system. Melanoma and breast cancer cells with high MRTF expression were selectively eliminated by cytotoxic lymphocytes in mouse models of metastasis. This immunosurveillance phenotype was further enhanced by treatment with immune checkpoint blockade (ICB) antibodies. We also observed that high MRTF signaling in human melanoma is associated with ICB efficacy in patients. Using biophysical and functional assays, we showed that MRTF overexpression rigidified the filamentous actin cytoskeleton and that this mechanical change rendered mouse and human cancer cells more vulnerable to cytotoxic T lymphocytes and natural killer cells. Collectively, these results suggest that immunosurveillance has a mechanical dimension, which we call mechanosurveillance, that is particularly relevant for the targeting of metastatic disease. © 2021 Elsevier Inc.
Keywords: metastasis; cytotoxicity; immunosurveillance; t cell; cancer immunology; mechanobiology; nk cell; checkpoint blockade therapy; myocardin related transcription factor
Journal Title: Immunity
Volume: 54
Issue: 5
ISSN: 1074-7613
Publisher: Cell Press  
Date Published: 2021-05-11
Start Page: 1037
End Page: 1054.e7
Language: English
DOI: 10.1016/j.immuni.2021.02.020
PUBMED: 33756102
PROVIDER: scopus
PMCID: PMC8119359
DOI/URL:
Notes: Article -- Export Date: 1 June 2021 -- Source: Scopus
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MSK Authors
  1. Luc Morris
    281 Morris
  2. Katharine C Hsu
    186 Hsu
  3. Joan Massague
    389 Massague
  4. Morgan Huse
    68 Huse
  5. Umeshkumar Kapaldev Bhanot
    93 Bhanot
  6. Adrienne Boire
    109 Boire
  7. Yevgeniy Romin
    32 Romin
  8. Ekrem Emrah   Er
    9 Er
  9. Jing   Hu
    9 Hu
  10. Douglas Robert Hoen
    10 Hoen
  11. Jan Remsik
    25 Remsik
  12. Annalisa Calo
    4 Calo
  13. Katja Srpan
    6 Srpan