biostudies-literatureYu AHunan Natural Science FoundationNational Natural Science Foundation of ChinaGuangzhou Science and Technology ProjectsHunan Province Young Talents Programthe Natural Science Foundation of Guangdong Province, Chinae007230https://www.ebi.ac.uk/biostudies/studies/S-EPMC10565151biostudies-literatureUnknown11(10)<h4>Background</h4>Immune checkpoint inhibitor (ICI) therapy improves the survival of patients with advanced bladder cancer (BLCA); however, its overall effectiveness is limited, and many patients still develop immunotherapy resistance. The leucine-rich repeat and fibronectin type-III domain-containing protein (LRFN) family has previously been implicated in regulating brain dysfunction; however, the mechanisms underlying the effect of LRFN2 on the tumor microenvironment (TME) and immunotherapy remain unclear.<h4>Methods</h4>Here we combined bulk RNA sequencing, single-cell RNA sequencing, ProcartaPlex multiple immunoassays, functional experiments, and TissueFAXS panoramic tissue quantification assays to demonstrate that LRFN2 shapes a non-inflammatory TME in BLCA.<h4>Results</h4>First, comJournal for immunotherapy of cancerBladder cancer intrinsic LRFN2 drives anticancer immunotherapy resistance by attenuating CD8⁺ T cell infiltration and functional transition.PMC1056515181902576821036392023A1515030038820707852022010109102020JJ5884818736262021RC302781902592Li HShu GJing LHuang GZhang MDeng DHu JChen ZLuo JYu AZu XFu LChen XWang YYang TWei JfalseBladder cancer intrinsic LRFN2 drives anticancer immunotherapy resistance by attenuating CD8⁺ T cell infiltration and functional transition.<h4>Background</h4>Immune checkpoint inhibitor (ICI) therapy improves the survival of patients with advanced bladder cancer (BLCA); however, its overall effectiveness is limited, and many patients still develop immunotherapy resistance. The leucine-rich repeat and fibronectin type-III domain-containing protein (LRFN) family has previously been implicated in regulating brain dysfunction; however, the mechanisms underlying the effect of LRFN2 on the tumor microenvironment (TME) and immunotherapy remain unclear.<h4>Methods</h4>Here we combined bulk RNA sequencing, single-cell RNA sequencing, ProcartaPlex multiple immunoassays, functional experiments, and TissueFAXS panoramic tissue quantification assays to demonstrate that LRFN2 shapes a non-inflammatory TME in BLCA.<h4>Results</h4>First, com2023-01-01T00:00:00Z2023 Oct2026-06-15T06:34:15.476Z2025-02-18T23:52:21.817ZS-EPMC105651513780260310.1136/jitc-2023-007230