Core Framework & Diagram What Is Tumor Microenvironment?

Through tumor biopsy pathological analysis — immunohistochemistry (IHC) can detect CD8+ T cell density inside the tumor; flow cytometry can analyze ratios of various immune cell types; gene expression profiling (RNA sequencing) can assess immune-related gene activity. Clinically, PD-L1 expression levels and tumor mutation burden (TMB) are also commonly used proxy indicators.

Oncolytic viruses are engineered viruses that selectively infect and lyse cancer cells, simultaneously triggering local inflammatory reactions that 'ignite' the tumor to let immune cells flood in. This is precisely the strategy for warming cold tumors: use oncolytic virus to create local inflammation, break CAF barriers, recruit T cells, then combine with checkpoint inhibitors to further activate those T cells.

The hypoxic environment produced by tumor rapid growth drives tumors to massively secrete VEGF, promoting new blood vessel formation. But these new blood vessels form at extreme speed, creating very disordered structures — incomplete vessel walls, unstable blood flow, abnormal permeability. Anti-VEGF treatment's partial efficacy comes from 'normalizing' tumor vasculature, improving immune cell access channels into the tumor.

NK cells face multiple challenges in the TME: hypoxia and acidity reduce cytotoxicity; TGF-β downregulates activating receptors (NKG2D); adenosine via A2AR shuts off effector functions; CAF barriers block physical penetration. This is why NK cell therapy challenges are greater in solid tumors than blood tumors.

There's some evidence. Regular exercise has been found to reduce M2 macrophage proportions in tumor microenvironments and increase CD8+ T cell infiltration; controlling obesity reduces pro-inflammatory factors from fat tissue (IL-6, leptin), indirectly improving TME inflammatory balance; quitting smoking reduces tobacco compound damage to tumor microenvironment immune cell function.