Table 5 Metabolic-immune crosstalk in the TME of RCC.
From: The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma
Target | Molecular mechanism | Biological function | Reference |
|---|---|---|---|
miR-29b/miR-198 | Suppress JAK3 and MCL-1 expression in CD8+ T cells. | Impairs anti-apoptotic and proliferative capacity of CD8+ T cells; reversible via miRNA inhibition. | [119] |
Kynurenine (KYN) pathway | Elevated KYN-to-tryptophan (KTR) ratio depletes tryptophan and generates immunosuppressive metabolites. | Inhibits T cell function, promotes Treg expansion; correlates with poor survival (5-year CSS: 76.9% vs. 92.3%, P < 0.0001). | [120] |
Pentraxin-3 (PTX3) | Activates classical complement pathway (C1q/C3aR/C5aR) and upregulates CD59 to evade complement lysis. | Fosters pro-angiogenic niche (VEGF/IL-8 enrichment); drives M2 macrophage polarization and CD8+ T cell exclusion. | |
Bevacizumab | Inhibits VEGF and reduces microvascular density; depletes CD68+ macrophages and tryptase+ mast cells. | Disrupts stromal pro-angiogenic factor release; synergizes with immune modulation. | [118] |
Serum metabolomics | Baseline metabolic profiles predict immune checkpoint inhibitor (ICI) efficacy (>80% accuracy). | Enables patient stratification for personalized immunotherapy. | [123] |
C3aR/C5aR complement axis | Inhibition blocks angiogenesis and restores CD8+ T cell infiltration. | Dual therapeutic node: targets angiogenesis and immunosuppression. | [124] |
TME nutrient competition | Extracellular acidosis and nutrient scarcity drive CD8+ T cell exhaustion. | Promotes T cell dysfunction; tumor-associated fibroblasts secrete complement factors to sustain immunosuppression. | [125] |
