Harnessing Cuproptosis for Antitumor Immunity: A Review of Current Evidence and Therapeutic Strategies

ABSTRACT Immune checkpoint inhibitors (ICI) have transformed cancer therapy, yet patient response rates remain low across most tumor types, underscoring the need for strategies that enhance tumor immunogenicity. Cuproptosis, a recently characterized form of regulated cell death driven by intracellular copper accumulation and lipoylated protein aggregation, has emerged as a mechanistically distinct pathway with immunological implications that remain largely unexplored. In this review, we examine the evidence supporting cuproptosis as an inducer of immunogenic cell death, including its capacity to trigger damage‐associated molecular patterns, promote dendritic cell maturation, and remodel the immunosuppressive tumor microenvironment. The two principal copper ionophores, elesclomol and disulfiram, are discussed in the context of mechanistic studies and therapeutic relevance. We identify key mechanistic gaps and propose cuproptosis‐based combination strategies as a rational approach to expanding the ICI responsive patient population. Preclinical and clinical data across major cancer types are evaluated to identify the therapeutic relevance of cuproptosis. Through addressing these points, we conclude that cuproptosis is an under‐appreciated route for improving existing immunotherapies for cancer.