Session 2:  Microenvironment and resistance 

High endothelial venules (HEVs) : specialized blood vessels for lymphocyte entry in tumors during cancer immunotherapy

Immunotherapy, a therapeutic strategy aimed at increasing the activity of the immune system, has revolutionized cancer treatment over the past decade. A better understanding of how this therapeutic approach works, and more particularly how killer lymphocytes access tumors during immunotherapy, could improve the efficacy of the treatments. We recently discovered the essential role played in this process by specialized blood vessels known as tumor-associated high endothelial venules (TA-HEVs) (Asrir* et al. Cancer Cell 2022). TA-HEVs share important phenotypic and functional characteristics with HEVs in lymph nodes and other lymphoid organs (Moussion and Girard, Nature 2011 ; Girard et al, Nature Rev Immunol 2012). For the first time, we were able to film the lymphocytes infiltrating TA-HEV walls to enter the tumors. We found that increasing the proportion of TA-HEVs in a tumor improves the infiltration of stem-like CD8+ T cells, the efficacy of the immunotherapy and leads to the eradication of the tumors. Finally, we showed that the likelihood of recovery of metastatic melanoma patients treated with anti-PD-1 plus anti-CTLA-4 immunotherapy is increased when a large number of TA-HEVs are present in tumors. Together our results suggest that increasing the density of TA-HEVs in human tumors could increase lymphocyte infiltration, making immunotherapy effective in a greater number of patients.