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

• Published in: Communications biology Vol. 5; no. 1; pp. 1416 - 16
• Main Authors: Devi-Marulkar, Priyanka, Fastenackels, Solène, Karapentiantz, Pierre, Goc, Jérémy, Germain, Claire, Kaplon, Hélène, Knockaert, Samantha, Olive, Daniel, Panouillot, Marylou, Validire, Pierre, Damotte, Diane, Alifano, Marco, Murris, Juliette, Katsahian, Sandrine, Lawand, Myriam, Dieu-Nosjean, Marie-Caroline
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.12.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/21; 13/31; 13/51; 14/1; 38; 38/61; 631/250/1619/554/1898/1271; 631/250/2520; 631/250/580; 631/67/1612/1350; Biology; Biomedical and Life Sciences; Carcinoma, Non-Small-Cell Lung - pathology; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Cell proliferation; CTLA-4 protein; Cytokines; Cytotoxicity; Dendritic cells; Glucocorticoids; Humans; Immune checkpoint; Immunoregulation; Immunosuppressive agents; Life Sciences; Lung cancer; Lung Neoplasms - pathology; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating; Non-small cell lung carcinoma; Small cell lung carcinoma; Solid tumors; T-Lymphocytes, Regulatory; Tertiary Lymphoid Structures - metabolism; Tertiary Lymphoid Structures - pathology; Tumor necrosis factor receptors; Tumor-infiltrating lymphocytes
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-04356-y

On 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. Regulatory T cells (Tregs) have similar immune profiles in tertiary lymphoid structures of lung cancer and non-TLS areas, with tumor-infiltrating Tregs found to inhibit the proliferation and cytokine secretion of CD4 + conventional T cells.