Molecular profiles of different PD-L1 expression in patients with esophageal squamous cell carcinoma

BACKGROUND: PD-1/PD-L1 inhibitors are approved treatments for patients with esophageal squamous cell carcinoma (ESCC). The present investigation aspired to explore the interrelation between molecular phenotype and PD-L1 expression in ESCC. METHODS: PD-L1 testing and targeted next-generation sequencing (NGS) were performed on tumoral tissues from 139 ESCC patients. Tumor-infiltrating lymphocytes (TILs) were scrutinized using a tyramide signal amplification system combined with immunohistochemistry. RESULTS: Among enrolled patients, 36.7% displayed high PD-L1 expression (combined positive score [CPS] ≥10). BRCA1 and NF1 gene mutations were significantly associated with high PD-L1 expression (p < .05) while TGFβ pathway alterations were linked to low PD-L1 expression (p = .02). High copy number instability (CNI) and copy number alterations (CNA) were correlated with low PD-L1 expression. Patients with CDKN2A deletion exhibited higher PD-L1 expression. Varying types of TILs were observed across different PD-L1 expression groups. The ratio of CD8(+)PD-L1(+) T cells and CD8(+)PD-1(+) T cells to CD8(+) T cells remained comparable in both tumoral and stromal regions, but the ratio of CD68(+)PD-L1(+) macrophages to CD68(+) macrophages was higher than the ratio of CD68(+)PD-1(+) macrophages to CD68(+) macrophages. CPS was significantly correlated with PD-L1(+) lymphocytes and CD68(+) macrophages in the tumoral region. CD8(+) T cell infiltration was positively correlated with PD-1(+) cells in both tumoral and stromal regions. CONCLUSION: In this study, we presented the prevalence rates of PD-L1 expression in Chinese ESCC patients. The association of genetic profiles with PD-L1 expression levels also provide the clue that genomic phenotype may interact with the immunologic phenotype in ESCC.