Journal
COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-022-04356-y
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Funding
- Institut National du Cancer [INCa-DGOS_10888]
- Sorbonne Universite
- Universite de Paris
- Fondation ARC pour la Recherche sur le Cancer
- La Ligue contre le Cancer
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Regulatory T cells (Tregs) play a role in tumor immunity, but Tregs in tertiary lymphoid structures (TLS) have similar immune characteristics to those in non-TLS areas. Tumor-infiltrating Tregs inhibit conventional T cell proliferation, but this inhibition can be restored by antibodies against CTLA-4 and GITR. Tregs in the whole tumor are associated with a poor outcome in NSCLC patients, while combined use with TLS-DCs and CD8(+) T cells improves overall survival.
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.
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