Upregulated TIGIT+ and Helios+ regulatory T cell levels in bronchoalveolar lavage fluid of NSCLC patients

Abstract

Background: The tumour microenvironment reshapes the specific gene expression of regulatory T cells (Tregs). A better definition of Treg subpopulations in the non-small-cell lung cancer (NSCLC) milieu is expected to clarify the identity and functional mode of Tregs and lead to the identification of better therapeutic targets.

Methods: A total of 53 peripheral blood (PB) samples from 36 NSCLC patients and 17 control subjects and 42 matched bronchoalveolar lavage fluid (BALF) samples from 31 NSCLC patients and 11 control subjects were obtained to examine the frequencies of Treg subgroups through flow cytometry. Fifteen PB samples from healthy individuals were collected to explore the differential functions of Treg subsets. The PB samples of 5 patients after chemotherapy were obtained to evaluate the effect of chemotherapy on Treg subsets. Serum CYFRA 21-1 levels in NSCLC patients were determined using an electrochemiluminescence immunoassay.

Results: The proportions of CD4⁺CD25⁺FoxP3⁺ Tregs in both PB and BALF were increased in NSCLC patients compared to controls. In BALF, the TIGIT⁺, Helios⁺, and TIGIT⁺Helios⁺ Treg subset levels were significantly elevated; the levels of the last two subsets were associated with NSCLC development, while the level of TIGIT^-Helios^- Tregs was decreased. The proportions of overall Tregs and TIGIT⁺, Helios⁺, and Helios⁺TIGIT⁺ Tregs were positively correlated with the serum CYFRA 21-1 levels in all patients. Functional differences were observed between Helios⁺TIGIT⁺ and Helios^-TIGIT^- Tregs. After chemotherapy, regardless of the reduction in serum CYFRA 21-1 levels, the proportions of Tregs and Treg subsets did not change.

Conclusions: Elevated TIGIT⁺Helios⁺ and Helios⁺ Treg levels may play a role in NSCLC tumour progression, and targeting TIGIT and Helios on Tregs may be an effective treatment for NSCLC.

Keywords: Helios; Non-small-cell lung cancer; Regulatory T cells; TIGIT.