Cytotoxic lymphocytes use mechanosurveillance to target biophysical vulnerabilities in cancer

التفاصيل البيبلوغرافية
العنوان: Cytotoxic lymphocytes use mechanosurveillance to target biophysical vulnerabilities in cancer
المؤلفون: Katja Srpan, Yevgeniy Romin, Katharine C. Hsu, Ekrem Emrah Er, Maria Tello-Lafoz, Jing Hu, Morgan Huse, Annalisa Calò, Joan Massagué
بيانات النشر: Cold Spring Harbor Laboratory, 2020.
سنة النشر: 2020
مصطلحات موضوعية: 0303 health sciences, Cancer, Biology, Actin cytoskeleton, medicine.disease, Immune checkpoint, Immunosurveillance, 03 medical and health sciences, 0302 clinical medicine, Immune system, Myocardin, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, medicine, Cytotoxic T cell, 030304 developmental biology
الوصف: Immune cells identify cancer cells by recognizing characteristic biochemical features indicative of oncogenic transformation. Cancer cells have characteristic mechanical features, as well, but whether these biophysical properties also contribute to destruction by the immune system is not known. In the present study, we found that enhanced expression of myocardin related transcription factors (MRTFs), which promote migration and metastatic invasion, paradoxically compromised lung colonization by melanoma and breast carcinoma cells in an immune-mediated manner. Cancer cells with increased MRTF signaling were also more sensitive to immune checkpoint blockade therapy in mice and humans. The basis for this vulnerability was not biochemical, but biophysical. MRTF expression strengthened the actin cytoskeleton, increasing the rigidity of cancer cells and thereby making them more vulnerable to cytotoxic T lymphocytes and natural killer cells. These results reveal a mechanical dimension of immunosurveillance, which we call mechanosurveillance, that is particularly relevant to the targeting of metastatic disease.
اللغة: English
DOI: 10.1101/2020.04.21.054304
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c3b69f6f8867d0546d57c09139caacc
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....8c3b69f6f8867d0546d57c09139caacc
قاعدة البيانات: OpenAIRE
الوصف
DOI:10.1101/2020.04.21.054304