The transcription factor Blimp-1 is suppressed by SLAMF1 and drives Treg cell-mediated immune evasion in non-small cell lung cancer.

Abstract

Background: Immune checkpoint inhibitors targeting the interaction between PD1 and PDL1 are effective for immunotherapy in non-small cell lung cancer (NSCLC). However, only subgroups of patients respond to therapy, suggesting the existence of resistance mechanisms.

Methods: In this study, we analyzed post-surgery lung tissues and peripheral blood cells from patients with Non Small Cell Lung Cancer (NSCLC) and control subjects by using western blot, immunohistochemistry, ELISA, multiplex cytokine, and qPCR analysis.

Results: Here, we found progressively increased Blimp1 expression in the tumoral region of NSCLC patients, where Slamf1 significantly decreased, and it inversely correlated with Blimp1. In PBMCs, Blimp1 was expressed in CD8+ T cells but predominantly in immunosuppressive Foxp3+ Treg cells or after targeting of the T cell activator Slamf1. Anti-CD3/CD28 induced IL-6 and IL-10, an immunosuppressive gene induced by Blimp1, in the supernatants of PBMCs from patients with NSCLC. Targeting PD1 in PBMCs reduced Blimp1.

Conclusions: Here, we identify a key role of the transcription factor Blimp1 for immune evasion in NSCLC. Thus, targeting Blimp1 emerges as a novel concept to improve current lung cancer immunotherapies and to suppress immune evasion in lung cancer.