To discuss ccRCC immunotherapy response from an immune-ecological perspective and to explore treatment-relevant immune states.
Approach:
Immune-Ecological Perspective: Focus on treatment-relevant immune states in ccRCC, including dysfunctional T-cell-inflamed tumors, myeloid-dominant suppressive tumors, angiogenesis- and hypoxia-skewed tumors, and immune-excluded tumors.
Multi-Omics Technologies: Utilize bulk transcriptomics, single-cell and spatial profiling, T-cell receptor sequencing, proteomics, metabolomics, and longitudinal liquid biopsy to define immune ecotypes and capture treatment-induced remodeling.
Key Findings:
High CD8+ T-cell infiltration in ccRCC does not always correlate with effective antitumor immunity.
Current biomarkers such as PD-L1, TMB, and IMDC risk classification are insufficient alone for reliable treatment selection.
An immune ecology framework can help interpret the relationships between tumor cells, immune populations, and the microenvironment.
Interpretation:
The immune-ecotype framework provides a broader context for understanding biomarker variability.
Limitations:
Established biomarkers may conflict in practice and do not fully capture the complexity of ccRCC biology.
PD-L1 immunohistochemistry is confounded by various factors and has not reliably predicted ICI benefit in ccRCC.
Conclusion:
The integration of established biomarkers within an immune-ecotype framework may enhance the understanding of treatment responses in ccRCC.
