Targeting regulated cell death: Apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity.

Abstract

In the evolving landscape of cancer treatment, the strategic manipulation of regulated cell death (RCD) pathways has emerged as a crucial component of effective anti-tumor immunity. Evidence suggests that tumor cells undergoing RCD can modify the immunogenicity of the tumor microenvironment (TME), potentially enhancing its ability to suppress cancer progression and metastasis. In this review, we first explore the mechanisms of apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis, along with the crosstalk between these cell death modalities. We then discuss how these processes activate antigen-presenting cells, facilitate the cross-priming of CD8+ T cells, and trigger anti-tumor immune responses, highlighting the complex effects of novel forms of tumor cell death on TME and tumor biology. Furthermore, we summarize potential drugs and nanoparticles that can induce or inhibit these emerging RCD pathways and their therapeutic roles in cancer treatment. Finally, we put forward existing challenges and future prospects for targeting RCD in anti-cancer immunity. Overall, this review enhances our understanding of the molecular mechanisms and biological impacts of RCD-based therapies, providing new perspectives and strategies for cancer treatment.