Core Framework & Diagram How Does the Tumor ‘Turn Off’ Immune Switches?

Not 'better' but 'supplementary for different scenarios.' PD-1 inhibitors remain the strongest-efficacy, best-understood choice in suitable patients. The significance of new targets like LAG-3 and TIM-3 is: combined with PD-1, providing new options for PD-1 monotherapy non-responders or resistant patients; more precise activity in patients with specific molecular features (like LAG-3+/PD-1+ co-expression).

PD-L1 positivity is only one of many response-affecting factors. If PD-L1 positivity comes from 'intrinsic expression' (driven by tumor cell's own genetic changes) rather than 'adaptive expression' (induced by T cell-secreted IFN-γ), it suggests the tumor may have essentially no T cells fighting inside it — releasing the PD-1 brake has no T cells to liberate. Additionally, other immunosuppressive mechanisms (LAG-3 co-expression, high TGF-β, adenosine pathway) may simultaneously exist.

The fundamental difference is in target. Targeted therapy (like anti-HER2, anti-EGFR) directly attacks driver mutation proteins on cancer cell surfaces, blocking pro-tumor signaling pathways — acts on cancer cells themselves. Immune checkpoint inhibitors don't directly attack cancer cells but act on immune cells (T cells), releasing the 'immune brakes' tumors installed, letting the immune system self-identify and eliminate cancer cells.

Through tumor biopsy pathological analysis — immunohistochemistry (IHC) detects CD8+ T cell density inside the tumor; gene expression profiling assesses immune-related gene activity; and TMB (high TMB usually corresponds to more neoantigens and more likely hot tumor). Pancreatic cancer, prostate cancer, brain glioma are typically cold tumors; melanoma and high MSI colorectal cancer are typically hot tumors.