Regulatory T cells infiltrate the tumor-induced tertiary lymphoïd structures and are associated with poor clinical outcome in NSCLC

• DOI: 10.1038/s42003-022-04356-y
• Publication Date: 2022-12-24T12:02:43Z
• Authors: Priyanka Devi-Mar...; Solène Fastenackels; Pierre Karapentiantz; Jérémy Goc; Claire Germain; Hélène Kaplon; Samantha Knockaert; Daniel Olive; Marylou Panouillot; Pierre Validire; Diane Damotte; Marco Alifano; Juliette Murris; Sandrine Katsahian; Myriam Lawand; Marie-Caroline Di...
• Keywords: 0303 health sciences; Lung Neoplasms; QH301-705.5; [SDV]Life Sciences [q-bio]; 610; CD8-Positive T-Lymphocytes; T-Lymphocytes, Regulatory; Article; 3. Good health; [SDV] Life Sciences [q-bio]; 03 medical and health sciences; Tertiary Lymphoid Structures; Lymphocytes, Tumor-Infiltrating; Carcinoma, Non-Small-Cell Lung; Humans; Biology (General)

AbstractOn one hand, regulatory T cells (Tregs) play an immunosuppressive activity in most solid tumors but not all. On the other hand, the organization of tumor-infiltrating immune cells into tertiary lymphoid structures (TLS) is associated with long-term survival in most cancers. Here, we investigated the role of Tregs in the context of Non-Small Cell Lung Cancer (NSCLC)-associated TLS. We observed that Tregs show a similar immune profile in TLS and non-TLS areas. Autologous tumor-infiltrating Tregs inhibit the proliferation and cytokine secretion of CD4+ conventional T cells, a capacity which is recovered by antibodies against Cytotoxic T-Lymphocyte-Associated protein-4 (CTLA-4) and Glucocorticoid-Induced TNFR-Related protein (GITR) but not against other immune checkpoint (ICP) molecules. Tregs in the whole tumor, including in TLS, are associated with a poor outcome of NSCLC patients, and combination with TLS-dendritic cells (DCs) and CD8+ T cells allows higher overall survival discrimination. Thus, Targeting Tregs especially in TLS may represent a major challenge in order to boost anti-tumor immune responses initiated in TLS.