Journal: Nature cancer
This study used multi-omics profiling (proteomics, phosphoproteomics, genomics, and transcriptomics) in 240 patients with nasopharyngeal carcinoma treated with either gemcitabine–cisplatin induction chemotherapy (GP-IC) or concurrent chemoradiotherapy (CCRT) alone.
Key points:
- Three proteomic subtypes were identified with distinct treatment sensitivities:
- S1: Dominant interferon-γ response; these patients had good outcomes with CCRT alone, suggesting GP-IC may be unnecessary.
- S2: Characterized by copy number–driven cell cycle activation; these patients derived clear benefit from adding GP-IC.
- S3: Immune-exhausted phenotype with high IgA plasma cell infiltration; these tumors were resistant to GP-IC but responded to anti–PD-1 therapy.
- Single-cell RNA sequencing showed functional interaction between IgA plasma cells and CD8 T cells in patients who did not respond to GP-IC.
- Validation across three phase III trials and spatial analyses confirmed that:
- High IgA plasma cell infiltration predicts resistance to GP-IC.
- The same feature is associated with benefit from anti–PD-1 therapy.
Overall, the work proposes a subtype-based framework to guide choice among CCRT alone, GP-IC plus CCRT, and immunotherapy in nasopharyngeal carcinoma, using tumor proteomic/immune features—particularly IgA plasma cell infiltration—as predictive markers.