接受免疫治疗的黑色素瘤患者中淋巴细胞和免疫通路的肿瘤图谱

Tumor-infiltrating lymphocytes (TILs) shape melanoma behavior and response to immunotherapy, but the links between immune regulation, TIL patterning, and outcomes remain unclear.

We retrospectively studied 32 primary melanoma samples from patients treated with anti-PD-1 therapy. Histopathologic TILs were classified as brisk or non-brisk, and primary tumors underwent targeted immune transcriptomic profiling (NanoString nCounter Human Immunology panel). External validation was performed with 96 TCGA-SKCM primary tumors. Brisk tumors displayed broad upregulation of immune transcripts, with enrichment of adhesion pathways (directed global significance scores - DGSS = 2. 15) and MHC class II antigen presentation (DGSS = 2. 128). Cross-cohort comparison identified 22 shared differentially expressed genes, with ZAP70 remaining significant in both datasets.

Brisk tumors also showed higher total TIL (p = 0. 036), cytotoxic-cell (p = 0. 0095), and Th1 (p = 0. 027) scores. Response-associated genes differed by TIL pattern, and subgroup-specific gene scores predicted anti-PD-1 benefit in brisk (4-gene, Area under curve - AUC = 1. 000) and non-brisk (3-gene, AUC = 0.

852) tumors; the non-brisk score remained independently associated with response (p = 0. 029). Higher scores were also associated with prolonged survival. Integrating histopathological TIL patterning with immune transcriptomics may refine prognostication and support immunotherapy stratification in melanoma.