Inhibition of MBTPS1 enhances antitumor immunity and potentiates anti-PD-1 immunotherapy

ABSTRACT: In this project, we transfected MC38 cells with Flag-tagged Mbtps1 or vector control. After that, we performed immunoprecipitation–mass spectrometry analysis to search the interacting proteins of MBTPS1. In our study, We observed that the loss of membrane-bound transcription factor site-1 protease (MBTPS1) in tumor cells enhanced antitumor immunity and potentiated anti-PD-1 therapy. Mechanistic studies revealed that tumor cell-intrinsic MBTPS1 competed with USP13 for binding to STAT1, thereby disrupting USP13-dependent deubiquitination and stabilization of STAT1. MBTPS1 deficiency induced CXCR3+ CD8+ T cell infiltration by upregulating STAT1-transcribed chemokines including CXCL9, CXCL10 and CXCL11. Notably, the regulatory role of MBTPS1 in antitumor immunity operates independently of its classic function in cleaving membrane-bound transcription factors. Collectively, our results provide a theoretical basis for MBTPS1 as a potential immunotherapy target and also as a predictor of immunotherapy efficacy.

INSTRUMENT(S):

ORGANISM(S): Arabidopsis Thaliana (mouse-ear Cress) Mus Musculus (mouse)

TISSUE(S): Malignant Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Yi-yu Wang  

LAB HEAD: Rui-hua Xu

PROVIDER: PXD053978 | Pride | 2025-04-11

REPOSITORIES: Pride