Tumor-infiltrated double-negative regulatory T cells predict outcome of T cell-based immunotherapy in nasopharyngeal carcinoma.

ABSTRACT: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has demonstrated clinical success in solid tumors. We analyze 47 TIL infusion products and 62 pretreatment tumor microenvironments (TMEs) from a randomized phase 2 clinical study of concurrent chemoradiotherapy plus TIL-ACT (NCT02421640). Using single-cell and bulk RNA sequencing along with flow cytometry, we identify 14 CD3⁺ T cell clusters within 26 TIL infusion products: 11 CD3⁺CD8⁺ TILs, 2 CD3⁺CD4⁺ TILs, and 1 CD3⁺CD8^-CD4^- double-negative (DN) TIL. (DN) TILs, significantly associated with poor TIL-ACT outcomes, exhibit an activated regulatory T cell-like phenotype and include two CD56⁺ and four CD56^- subset

SUBMITTER: Liu XF 

PROVIDER: S-EPMC12147895 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature