Mitochondria and Tumor Microenvironment Publisher



Taghizadehhesary F ; Bitarafan F
Source: Mitochondria and Cancer: From Basic Science to Clinical Applications - Understanding Pathogenesis, Therapy Resistance, and Disease Relapse Published:2026

Abstract

The tumor microenvironment (TME) is a dynamic and complex network composed of cancer cells, immune cells, stromal components, extracellular matrix, and various signaling molecules. It plays a pivotal role in shaping cancer pathogenesis, influencing tumor growth, immune evasion, metastasis, and response to therapy. Within this multifaceted niche, mitochondria—the central organelles responsible for cellular metabolism, redox balance, and apoptotic signaling—have emerged as critical regulators of both tumor cell behavior and the surrounding microenvironment. Evidence has illuminated the intricate interplay between mitochondria and components of the TME, revealing that mitochondrial function extends beyond energy production. This review explores emerging themes in the crosstalk between mitochondria and the TME, including mitochondria-mediated immune modulation, metabolic coupling between stromal and cancer cells, and the impact of mitochondrial transfer and biogenesis on tumor progression and therapy resistance. Key findings highlight the bidirectional communication between these systems and underscore mitochondria as potential therapeutic targets to reprogram the TME toward a more anti-tumorigenic state. Future research should aim to delineate the spatial and temporal orchestration of mitochondrial functions within different TME compartments and exploit this knowledge to develop mitochondria-targeted strategies that synergize with immunotherapies and conventional treatments. © 2026 Elsevier Inc. All rights reserved.