Decoding the impact of genetic variation on anti-tumoral immunity and immunotherapy efficacy in brain metastatic tumors

Brain metastases (BrMs) are the most common brain tumors in adults, and are linked to a dismal prognosis. Therefore, there is an urgent need for more effective treatments. Previous research linked the genetic makeup of cancer cells to the abundance and function of immune cells in the microenvironment of human BrMs, suggesting an important role for somatic variation in shaping the TIME. Our hypothesis is that genetic variation instructs specific immunophenotypes in the microenvironment of BrM tumors, which in turn shape responses to therapy.
Therefore, this project aims to:
(i) evaluate the efficacy of radio- and ICB therapy in preclinical mouse models of lung- and melanoma-BrM bearing different genetic makeups;
(ii) characterize the TIME in treated and untreated tumors from these models;
(iii) explore the link between somatic genetic variation, TIME phenotypes and responses to therapy in human BrMs.