Cystathionine-β-synthase (CBS) is a key metabolic enzyme traditionally associated with homocysteine metabolism. Recent studies have uncovered its broader role in tumor biology,1 yet its impact on the tumor immune microenvironment remains largely unexplored. Tumor immunotherapy has rapidly advanced, with strategies such as immune checkpoint inhibitors, chimeric antigen receptor-T cell therapy, and tumor vaccines revolutionizing cancer treatment. Extensive analyses have summarized these approaches and their underlying mechanisms.2 However, metabolic regulators like CBS may also contribute to tumor immune escape, offering novel therapeutic targets. Here, we report for the first time that CBS promotes tumor immune evasion by destabilizing major histocompatibility complex class I (MHC-I) molecules, revealing a previously unrecognized link between tumor metabolism and immune surveillance.