doi:10.70996/cip.00004

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癌症免疫观点 ›› 2025, Vol. 1 ›› Issue (1) : 31-42. DOI: 10.70996/cip.00004

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The Tumor Microenvironment as a Driver of Immune Escape and Therapeutic Resistance in Cancer

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Abstract

Tumor microenvironment (TME) has been at the center of defining cancer progression, immune evasion, and cancer response to treatment. The TME is an active network of immune cells and stromal cells, endothelial cells, extracellular matrix and soluble mediators that actively influence tumor behavior, rather than being a passive backdrop. This systematic review discusses the role of the TME in the immune escape induced by cellular immunosuppression (T-regs, TAMs, MDSCs), molecular signaling (cytokines, checkpoint ligands), stromal barriers, hypoxia and metabolic reprogramming. Simultaneously, the TME promotes therapeutic resistance to the immune checkpoint inhibitors, targeted therapies, chemotherapy, and adoptive T-cell therapy by restricting immune cell invasion and causing T-cell exhaustion. A systematic literature review revealed 58 quality publications that report on mechanisms of the TME-based resistance and analyze the imaginative approaches to TME remodelling. It has been demonstrated that immunotherapy with TME components, including VEGF, TGF-b, CSF-1R or metabolic enzymes, is more effective. The most promising ones are combination modalities that prevent immune checkpoints and reprogram the TME at the same time. It is important to know that the TME is a dynamic contributor to immune dysfunction and resistance to create a more robust and tailored cancer therapy.

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Tumor microenvironment / immune escape / therapeutic resistance / T-regs / cytokines / immunotherapy

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[J]. 癌症免疫观点. 2025, 1(1): 31-42 https://doi.org/10.70996/cip.00004

Wei Zhang, Fang Wang.

The Tumor Microenvironment as a Driver of Immune Escape and Therapeutic Resistance in Cancer

[J]. Cancer Immuno Perspectives. 2025, 1(1): 31-42 https://doi.org/10.70996/cip.00004

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