Table 5.

Mechanisms of innate and adaptive immune interactions in the CRC tumor–stroma microenvironment.

Mechanism	Key Components	Effect	Key Details
The secretion of pro-inflammatory cytokines	CAFs and TAMs	Induces inflammation	CAFs and TAMs secrete IL-6 and TNF-α, which can foster chronic inflammation, paradoxically promoting tumor progression.
The secretion of immunosuppressive factors	CAFs and TAMs	Immunosuppression	CAFs and TAMs secrete TGF-β, IL-10, and PD-L1, which inhibit T cells and promote Tregs.
T cell exhaustion	T cells	Immunosuppression	Chronic exposure to tumor antigens and inflammatory signals can lead to a state of T cell dysfunction characterized by sustained expression of inhibitory receptors (PD-1 and CTLA-4).
The recruitment of regulatory immune cells	MDSCs and Tregs	Immunosuppression	The tumor stroma can attract immunosuppressive cell types like MDSCs and Tregs, which suppress cytotoxic T cells and NK cells.
Metabolic reprogramming	Tumor cells and stromal cells	Immunosuppression	Tumor cells and stromal cells can alter the metabolic landscape of the TME, creating conditions like hypoxia and nutrient deprivation that negatively impact immune cell function.
The modulation of extracellular matrix (ECM)	CAFs	Creates a physical barrier	CAFs can remodel the ECM, creating a physical barrier that hinders immune cell infiltration and access to tumor cells.
Cell polarization	TAMs, CD4+ T cells, MDSCs, and DCs	Immunosuppression	TAMs adopt an M2 polarization state, CD4+ T cells can be polarized into Tregs, MDSCs suppress T cell function, and DCs can become tolerogenic.