TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory
Menée à l'aide de lignées cellulaires, de modèles murins et d'échantillons tumoraux fixés au formaldéhyde et inclus en paraffine après prélèvement sur des patients atteints d'un gliome infiltrant du tronc cérébral, cette étude démontre que l'inhibition du point de contrôle immunitaire TIM-3 favorise la régression tumorale et le développement d'une mémoire immunitaire antitumorale
Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain stem tumor and the leading cause of pediatric cancer-related death. To date, these tumors remain incurable, underscoring the need for efficacious therapies. In this study, we demonstrate that the immune checkpoint TIM-3 (HAVCR2) is highly expressed in both tumor cells and microenvironmental cells, mainly microglia and macrophages, in DIPG. We show that inhibition of TIM-3 in syngeneic models of DIPG prolongs survival and produces long-term survivors free of disease that harbor immune memory. This antitumor effect is driven by the direct effect of TIM-3 inhibition in tumor cells, the coordinated action of several immune cell populations, and the secretion of chemokines/cytokines that create a proinflammatory tumor microenvironment favoring a potent antitumor immune response. This work uncovers TIM-3 as a bona fide target in DIPG and supports its clinical translation.
Cancer Cell 2023