Immunogenic Cell Death in Canine Lung Cancer: A Comparative Veterinary Oncology (Review of Animal Models and Human NSCLC)

Primary canine lung carcinoma is uncommon but clinically aggressive and may provide a spontaneous, immunocompetent model for human non-small cell lung cancer (NSCLC).This review evaluated evidence that targeted therapies induce immunogenic cell death (ICD) across human, canine, and murine lung cancer models and examined conserved tumor-microenvironment barriers to ICD-driven immunity.PubMed, Scopus, and Web of Science were searched for peer-reviewed studies published from January 2000 to June 2026 that assessed canonical ICD hallmarks-calreticulin exposure, ATP release, HMGB1 release, or type I interferon signaling-after targeted therapy.Eligible studies were synthesized narratively and comparatively.Seventy-five studies were synthesized.Results are organized into five thematic areas: (1) canine lung carcinoma as a spontaneous veterinary disease model, (2) veterinary and companion-animal evidence relevant to ICD, (3) human NSCLC evidence as a comparative reference, (4) conserved immune and stromal barriers across species and (5) animal-model evidence informing future veterinary trials.The synthesis reveals that while the molecular machinery for ICD induction and sensing is highly conserved, the tumor microenvironment-dominated by macrophage-mediated efferocytosis-constitutes the critical rate-limiting checkpoint for translating ICD into anti-tumor immunity across all species examined.Available evidence supports cross-species conservation of major ICD pathways and suggests that canine lung cancer may be useful for investigating mechanisms that limit ICD-driven immunity.Nevertheless, the reproducibility, clinical relevance, and therapeutic benefit of combining ICD-inducing agents with microenvironment-targeted treatments in dogs remain uncertain and require validation in larger, controlled prospective studies.