FGFR3 Alterations in Bladder Cancer Stimulate Serine Synthesis to Induce Immune-Inert Macrophages That Suppress T-cell Recruitment and Activation.

ABSTRACT: FGFR3 alterations are common in patients with bladder cancer. While the FGFR tyrosine kinase inhibitor erdafitinib has been approved as a targeted therapy for patients with FGFR3-altered (aFGFR3) bladder cancer, the response rate remains suboptimal, prompting development of strategies to improve treatment response. Here, we observed an immune-desert tumor microenvironment (TME) phenotype in human aFGFR3 bladder cancer and demonstrated that mutant FGFR3 indirectly induces a "cold" TME in mouse bladder cancer models. Single-cell RNA sequencing revealed the central role of macrophages in inducing the cold TME of aFGFR3 tumors. Macrophages in aFGFR3 tumors exhibited reduced T-cell recruitment and antigen presentation capabilities. Increased serine synthesis in bladder cancer cells that was ind

SUBMITTER: Ouyang Y 

PROVIDER: S-EPMC10722136 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature