ECS & Cancer: Tumour Microenvironment, Immune Evasion, and Apoptosis

Cancer progression is increasingly recognised as a systems-level process driven not only by genetic alterations, but by persistent failures in immune coordination, inflammatory resolution, metabolic governance, and programmed cell death. Within this context, the tumour microenvironment (TME) emerges as a stabilising niche that supports immune evasion, stress tolerance, and resistance to apoptotic elimination. This paper examines the role of the Endocannabinoid System (ECS) as a central regulatory network influencing tumour–host interactions across the immune, metabolic, and apoptotic domains. The ECS is a conserved signalling system integrating GPCR-mediated lipid signalling, inflammatory tone, neuro-immune communication, stress adaptation, and cellular survival thresholds. Dysregulation of ECS signalling is proposed to contribute to tumour persistence by biasing immune tolerance, shaping the tumour microenvironment, and altering programmed cell death decision pathways. Drawing on established literature and systems-level synthesis, this work explores how ECS modulation intersects with immune evasion, tumour-promoting inflammation, ER stress responses, autophagy–apoptosis balance, and mitochondrial stress tolerance. Rather than presenting isolated molecular mechanisms, the paper frames ECS dysfunction as a coordination failure that permits malignant states to stabilise and recur. This work is intended as a conceptual and mechanistic synthesis. Therapeutic frameworks and signalling models are presented for illustrative purposes to support systems reasoning and hypothesis generation, not as clinical recommendations. The paper contributes to a growing body of research positioning cancer as a disorder of biological governance and recoverability, and the ECS as a critical regulatory interface within that landscape.