ESTRO 2024 - Abstract Book

S5185

Radiobiology - Immuno-radiobiology

ESTRO 2024

Primary CAF cultures were established from freshly collected NSCLC lung tumors. CAFs at early passage were exposed to 1x18Gy or 3x6Gy radiation regimens, and the expression of different immunoregulatory cell associated and secreted signaling molecules was analyzed 24h and 120h post-IR. The analyses included release of immunogenic cell death (ICD) signals, interferon (IFN) type I responses, expression of immune checkpoint ligands and receptors, as well as secretion of soluble cytokines, chemokines and growth factors.

Results:

CAFs are able to survive to ablative radiation regimens, however they enter into a stage of premature cell senescence. Our data show that CAFs avoid apoptosis and do not contribute with ICD signals or IFN-I release to radiation-mediated tumor immunoregulation. Furthermore, secretion levels of relevant immunoregulatory cytokines and growth factors including TGF-b, IL-1b, IL-6, IL-10, TNFa, VEGF, CXCL10 and CXCL12 remain comparable between non-irradiated and radiation-induced senescent CAFs. However, radiation exposure regulates cell surface expression of some key immunoregulatory receptors, including CD73, CD276, OX40L or MHC-I.

Conclusion:

Our data suggest that CAFs are highly radioresistant and do not contribute to anti-tumor adjuvanticity by the release of danger signals or IFN-I secretion post-RT. The immune phenotype of normal CAFs and radiation-induced senescent CAFs is similar, however, the observed enhancement of some key cell surface checkpoint receptors on irradiated CAFs could contribute to the establishment of an enhanced immunosuppressive TME after radiotherapy.

Keywords: immunosuppression, checkpoint-receptors, ICD

2560

Mini-Oral

Immunomodulatory potential of radiotherapy with immunotherapy in a humanized mouse model

Morgane Cogels 1 , Ghanem Ghanem 2 , Dirk Van Gestel 1 , Mohammad Krayem 1

1 Institut Jules Bordet, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Radiation Oncology Department, Brussels, Belgium. 2 Institut Jules Bordet, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Laboratory of Clinical and Experimental Oncology (LOCE), Brussels, Belgium

Purpose/Objective:

The immunomodulatory effects of radiotherapy together with the ability of immunotherapies to overcome cancer immune-escape provide a strong rationale for radiotherapy and immune checkpoint inhibitor (ICI) combinations. However, while many preclinical studies show encouraging results, clinical trials have shown little benefits of the combination, indicating an urgent need to investigate the underlying mechanisms of radio-immunotherapy effects and their dependency on radiotherapy dose, fractionation, treatment volumes, and sequence in representative humanized immunocompetent preclinical models.