Tumor-Resident T Cells, Associated With Tertiary Lymphoid Structure Maturity, Improve Survival in Patients With Stage III Lung Adenocarcinoma

Abstract

Tertiary lymphoid structure (TLS) and tumor-resident memory T cells (T_RM) play crucial roles in the anti-tumor immune response, facilitating a good prognosis in patients with cancer. However, there have been no reports on the relationship between T_RM and TLS maturity. In this study, we detected T_RM and the maturity of TLS by immunofluorescence staining and analyzed the relationship between their distribution and proportion in patients with lung adenocarcinoma (LUAD). The proportion of T_RM within TLSs was significantly higher than that outside and was positively correlated with the survival of patients. In addition, the proportions of CD4⁺CD103⁺ T_RM and CD8⁺CD103⁺ T_RM were significantly increased with the gradually maturation of TLSs. We divided the patients into three levels (grade 1, grade 2, and grade 3) according to the presence of increasing maturation of TLSs. The proportion of CD103⁺ T_RM in grade 3 patients was significantly higher than that in grade 1 and grade 2 patients, suggesting a close relationship between CD103⁺ T_RM and TLS maturity. Furthermore, positive prognosis was associated with grade 3 patients that exhibited CD103⁺${\text{T}}_{\text{RM}}^{\text{High}}$ phenotype.

Keywords: B cell; TIL; TLS; TRM; lung adenocarcinoma.