Differential impact of lymphocytes on radiation response in autochthonous vs transplant murine sarcomas

Preclinical studies in transplant tumor models showing high cure rates with combined radiotherapy (RT) and immunotherapy have rarely translated to clinical success, and studies in autochthonous tumor models are limited. We hypothesized that lymphocytes differentially affect RT response in transplant vs autochthonous tumor models. Here, we compared tumor onset and growth delay after 0 or 20 Gy for autochthonous vs transplant soft tissue sarcomas in Rag2-/- mice lacking an adaptive immune system vs immune-intact Rag2+/- mice. While time to tumor onset did not differ between Rag2-/- and Rag2+/- mice in the autochthonous model, transplant tumor onset was significantly slower in immunocompetent mice. No transplant tumors in Rag2-/- mice or autochthonous tumors were cured by RT, whereas 32% of Rag2+/- mice with transplant tumors were cured. These results highlight the importance of including autochthonous tumors as complementary model systems to study the interplay between the immune system and RT response.