AUTHOR=Gorchs Laia , Hellevik Turid , Bruun Jack-Ansgar , Camilio Ketil-Andre , Al-Saad Samer , Stuge Tor-Brynjar , Martinez-Zubiaurre Inigo TITLE=Cancer-Associated Fibroblasts from Lung Tumors Maintain Their Immunosuppressive Abilities after High-Dose Irradiation JOURNAL=Frontiers in Oncology VOLUME=5 YEAR=2015 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2015.00087 DOI=10.3389/fonc.2015.00087 ISSN=2234-943X ABSTRACT=
Accumulating evidence supports the notion that high-dose (>5 Gy) radiotherapy (RT) regimens are triggering stronger pro-immunogenic effects than standard low-dose (2 Gy) regimens. However, the effects of RT on certain immunoregulatory elements in tumors remain unexplored. In this study, we have investigated the effects of high-dose radiotherapy (HD-RT) on the immunomodulating functions of cancer-associated fibroblasts (CAFs). Primary CAF cultures were established from lung cancer specimens derived from patients diagnosed for non-small cell lung cancer. Irradiated and non-irradiated CAFs were examined for immunomodulation in experiments with peripheral blood mononuclear cells from random, healthy donors. Regulation of lymphocytes behavior was checked by lymphocyte proliferation assays, lymphocyte migration assays, and T-cell cytokine production. Additionally, CAF-secreted immunoregulatory factors were studied by multiplex protein arrays, ELISAs, and by LC-MS/MS proteomics. In all functional assays, we observed a powerful immunosuppressive effect exerted by CAF-conditioned medium on activated T-cells (