Target profiling of organoplatinum(II) complex reveals role of protein tyrosine phosphatase 1B in modulating immunogenicity

Immunogenic cell death (ICD) inducers are valuable chemotherapeutic agents that elicit protective immune responses against tumors. However, the specific molecular targets directly associated with ICD remain less explored. Here, a Type II ICD inducer, Pt-ER, was validated as a bona fide ICD inducer with the ability to establish protection against colorectal cancer. Based on Pt-ER, several ICD-inducing photoactivable probes were designed to capture their potential targets. By integrating quantitative proteomics analysis, genetic method and biochemical assays, we identified that PTP1B is a direct target of Pt-ER and engages in ICD.