Supporting data for ‘Enhancing MHC‑I–Mediated Immunity by ICMT Inhibition and Personalizing Chemotherapy with Patient‑Derived Organoids in Ovarian Cancer’

In this study, we performed a genome-wide CRISPR knockout screen to discover novel MHC-I–specific negative regulators in ovarian cancer. Isoprenylcysteine carboxylmethyltransferase (ICMT) emerged from this screen as a key MHC-I–specific negative regulator. Genetic knockdown and pharmacological inhibition of ICMT significantly increased surface MHC-I expression without inducing PD-L1, thereby enhancing CD8⁺ T cell–mediated killing of ovarian cancer cells in vitro. In vivo, ICMT inhibition sensitized tumours to anti–PD-L1 therapy by upregulating MHC-I expression and promoting CD8⁺ T-cell infiltration. Consistent with these findings, ICMT expression was negatively correlated with GZMB⁺CD8⁺ cytotoxic T cells in clinical ovarian cancer samples. Mechanistically, ICMT regulated surface MHC-I abundance through proteasome-dependent degradation.Patient-derived organoids (PDOs) were employed as a preclinical platform for drug testing and precision oncology. To test its feasibility to guide individualized therapy, we successfully established PDOs from 28 surgically resected primary ovarian tumours and 12 malignant ascites samples from patients with ovarian cancer. These PDOs recapitulated the histopathological features of their matched tumours. Drug testing revealed marked intra-patient heterogeneity in responses to chemotherapy and targeted agents. In PDOs derived from primary ovarian cancers, in vitro drug sensitivity correlated with patients’ progression‑free survival and CA‑125 normalization, and this association persisted even at clinical recurrence. In contrast, for PDOs derived from recurrent tumours, PDO drug responses did not correlate with clinical outcomes. Beyond clinically approved agents, we evaluated antibody–drug conjugates and observed substantial inter-patient heterogeneity in PDO responses, which was further validated in the patient-derived xenograft model. Additionally, we identified tumour stiffness and monocyte infiltration as factors associated with successful PDO establishment.