Targeting SPHK1 in macrophages remodels the tumor microenvironment and enhances anti-PD-1 immunotherapy efficacy in colorectal cancer liver metastasis.

ABSTRACT:

Background

Colorectal cancer liver metastasis (CRLM) is characterized by an immunosuppressive microenvironment and a blunted response to immunotherapy. Notably, tumor-associated macrophages (TAMs) play a critical role in modulating immune responses and exhibit significant heterogeneity in CRLM. Sphingosine kinase 1 (SPHK1) serves as a pivotal kinase in maintaining the balance between ceramide and sphingosine-1-phosphate (S1P) levels. However, the effects of SPHK1 within TAMs on tumor immune evasion during CRLM remain elusive. This study aimed at investigating the role of TAM-intrinsic SPHK1 in tumor immunosuppressive microenvironment in CRLM.

Methods

SPHK1 expression levels in TAMs were estimated by immunofluorescence and bioinformatics analysis. Several animal models were e

SUBMITTER: Zhan Y 

PROVIDER: S-EPMC12531427 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature