Cell-type-specific regulated cell deaths in the tumor immune microenvironment

Cancer immunology and regulated cell deaths are closely connected fields that are reshaping our understanding of tumor progression and therapeutic response. Malignant cells adapt to oncogenic, metabolic, oxidative, and treatment-related stress, by strengthening survival programs and disabling pathways, such as apoptosis and ferroptosis. These adaptations promote tumor persistence, immune evasion, and therapy resistance, while the immune effects of cell death vary according to the death modalities, the identity of the dying cell, and the mechanisms governing sensing and clearance. Current evidence indicates that regulated cell deaths can expose tumor antigens, release damage-associated molecular patterns, activate antigen-presenting cells, and improve antitumor immunity, but it may also induce immune tolerance, tissue repair, chronic inflammation, or tumor recurrence. Important questions remain regarding how malignant, immune, stromal, and endothelial cells differ in their susceptibility to death; how post-death signals are spatially and temporally organized; and how these processes influence responses to immunotherapy. A cell-type-resolved framework is therefore needed to reconcile opposing effects and guide more precise therapeutic interventions.This Research Topic aims to define the cellular/molecular microenvironmental determinants, of regulated cell deaths across tumors and host cells, and to clarify how death-programs/post-death communications shape cancer immunity. It will address how apoptosis, ferroptosis, pyroptosis, necroptosis, cuproptosis, PANoptosis, NETosis, autophagy-dependent cell death, and emerging death programs influence tumor progression, immune recognition, and treatment resistance. The Research Topic will also examine whether selectively eliminating malignant or immunosuppressive cells, while preserving or strengthening protective immune effectors, can improve the durability of cancer therapy. Studies identifying predictive biomarkers, therapeutic vulnerabilities, effective combinations, and mechanisms of response or resistance are particularly encouraged.To gather further insights into cell-type-specific/context-dependent regulation of cell death within the tumor immune microenvironment, we welcome articles addressing, but not limited to, the following themes:•Genetic, epigenetic, metabolic, and post-translational mechanisms regulating death susceptibility or resistance in malignant, immune, stromal, and endothelial cells.•Cell-type-specific effects of apoptosis, ferroptosis, pyroptosis, necroptosis, cuproptosis, PANoptosis, NETosis, autophagy-dependent cell death, and emerging regulated cell-death programs.•Interactions between regulated cell deaths, tumor evolution, immune surveillance, immunosuppression, metastasis, and therapeutic resistance.•Post-death communications, including tumor-antigen release and presentation, damage-associated molecular pattern sensing, cytokine and lipid-mediator signaling, efferocytosis, and immune suppression.•Spatial and temporal organization of cell deaths, and post-death responses within primary tumors, metastatic sites, and treatment-altered microenvironments.•Natural products and derivatives, synthetic small molecules, repurposed drugs, biologics, nanomaterials, and targeted delivery systems that modulate regulated cell death.•Strategies for selectively eliminating malignant or tumor-supportive cells while preserving antitumor immune effector populations.•Combination approaches integrating cell-death modulation with immune checkpoint blockade, adoptive cell therapy, cancer vaccines, radiotherapy, chemotherapy, or targeted therapy.•Biomarkers, preclinical models, and translational frameworks for predicting therapeutic efficacy, toxicity, and durable immune responses.Appendix: This Research Topic welcomes Original Research, Reviews, and Mini Reviews. Topic editors: Xin Hu, Antonino Bruno Source: https://www.frontiersin.org/research-topics/85376/cell-type-specific-regulated-cell-deaths-in-the-tumor-immune-microenvironment