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).
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-HEV blood vessels are present in tumors.
- Asrir A*, Tardiveau C*, Coudert J*, Laffont R*, Blanchard L*, Bellard E, Veerman K, Bettini S, Lafouresse F, Vina E, Tarroux D, Roy S, Girault I, Molinaro I, Martins F, Scoazec JY, Ortega N, Robert C and Girard JP. Tumor-associated high endothelial venules (TA-HEVs) mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy. Cancer Cell, 2022, 40, 318–334 (*Co-first authors)
- Veerman K, Tardiveau C, Martins F, Coudert J, and Girard JP. Single-cell analysis reveals heterogeneity of high endothelial venules and differential regulation of genes controlling lymphocyte entry to lymph nodes. Cell Rep, 2019, 26:3116-3131
- Girard JP#, Moussion C and Forster R. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nature Rev Immunol, 2012, 12:762-773 (#Corresponding author)
- Moussion C and Girard JP. Dendritic cells control lymphocyte entry to lymph nodes via high endothelial venules. Nature, 2011, 479:542-546
Invité par Pierre-Olivier Couraud
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