Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLC - PubMed
2 days ago
- #Non-small cell lung cancer
- #Immunotherapy
- #Tumor microenvironment
- Immune checkpoint inhibitors (ICIs) targeting PD-1 axis have transformed mNSCLC treatment, but disease progression remains an issue.
- Study involved 103 mNSCLC patients (81 treated with ICIs), using single-cell spatial profiling to analyze tumor microenvironment (TME).
- Only CD8+ T cells (TILs) were associated with ICI efficacy, highlighting the importance of their interaction with cancer cells.
- CD39/CD103/Ki-67 positive TILs identified as exhausted yet functional tumor-reactive CD8+ T cells.
- Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts were independent unfavorable factors.
- High CD73 expression on cancer cells may confer ICI tolerance in EGFR/ALK-oncogene+ NSCLC via M2-TAM accumulation and abnormal angiogenesis.
- Findings aid in developing targeted therapeutic strategies for ICI-treated mNSCLC.