Matteo Morotti, Alizee J Grimm, Helen Carrasco Hope, Marion Arnaud, Mathieu Desbuisson, Nicolas Rayroux, David Barras, Maria Masid, Baptiste Murgues, Bovannak S Chap, Marco Ongaro, Ioanna A Rota, Catherine Ronet, Aspram Minasyan, Johanna Chiffelle, Sebastian B Lacher, Sara Bobisse, Clément Murgues, Eleonora Ghisoni, Khaoula Ouchen, Ribal Bou Mjahed, Fabrizio Benedetti, Naoill Abdellaoui, Riccardo Turrini, Philippe O Gannon, Khalil Zaman, Patrice Mathevet, Loic Lelievre, Isaac Crespo, Marcus Conrad, Gregory Verdeil, Lana E Kandalaft, Julien Dagher, Jesus Corria-Osorio, Marie-Agnes Doucey, Ping-Chih Ho, Alexandre Harari, Nicola Vannini, Jan P Böttcher, Denarda Dangaj Laniti, George Coukos
Expansion of antigen-experienced CD8+ T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer1 . Interleukin-2 (IL-2) acts as a key regulator of CD8+ cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability2,3 . Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses. Here we report that prostaglandin E2 (PGE2 ), a known negative regulator of immune response in the tumour microenvironment4,5 , is present at high concentrations in tumour tissue from patients and leads to impaired IL-2 sensing in human CD8+ TILs via the PGE2 receptors EP2 and EP4...
April 24, 2024: Nature