Fueling Immunotherapy Resistance: SSBP4 Links Tumor Cholesterol Biosynthesis to Immune Evasion

Immune checkpoint inhibitors (ICI) have had a transformative impact on cancer treatment. However, many patients still fail to respond to ICIs, underscoring the need to identify novel drivers of resistance. In this issue, Ou and colleagues identify single-stranded DNA binding protein 4 (SSBP4) as one such candidate, demonstrating that it promotes intratumoral cholesterol biosynthesis to suppress lymphocyte recruitment and enable immune evasion. This work therefore nominates SSBP4 as a novel metabolic target to enhance antitumor immunity and expand ICI efficacy. See related article by Ou et al., p. XX .