SPATA2 and CYLD Inhibit T Cell Infiltration into Colorectal Cancer Regulation of IFN-γ/STAT1 Axis

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Dec 19

PMID 36531014

Authors

Tze Guan Tan

Yulia Zybina

Cooper McKenna

Aleksandra Olow

Subhadra Jayaraman Rukmini

Michael Thomas Wong

Svetlana Sadekova

Alissa Chackerian

David Bauche

Affiliations

Soon will be listed here.

Abstract

Introduction: Colorectal cancer (CRC) is largely refractory to currently available immunotherapies such as blockade of programmed cell death protein-1 (PD-1).

Results: In this study, we identified SPATA2 and its protein partner CYLD as novel regulators of CXC-ligand 10 (CXCL10), a T-cell-attractant chemokine, in CRC. By specifically deleting SPATA2 and CYLD in human and mouse CRC cell lines, we showed that these two proteins inhibit STAT1 accumulation and activation and subsequently CXCL10 expression in tumor cells. At steady-state, STAT1 is highly ubiquitinated in a SPATA2/CYLD-dependent manner. Finally, we demonstrated that tumor-specific deletion of SPATA2 and CYLD enhances anti-PD-1 response .

Discussion: Our data suggest that SPATA2 and CYLD represent two potential novel targets for treatment of immune-excluded, PD-1-resistant tumors.

Citing Articles

Clinical and functional significance of SPATA2 in cancer particularly in LIHC.

Zhou Y, Geng S, Tang R, Yu H, Zhang A, Bai Y Sci Rep. 2025; 15(1):8392.

PMID: 40069269 PMC: 11897323. DOI: 10.1038/s41598-025-91386-1.

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