Purpose: B7-H3 has emerged as a promising target for cancer immunotherapy. We assessed the role of B7-H3 expression in tumour-infiltrating immune cells in non-small-cell lung cancer (NSCLC).
Methods: Tumour-infiltrating immune cell characterisation was performed by flow cytometry in a prospective cohort, whereas the relationship between B7-H3 expression and clinicopathological features was explored in a retrospective cohort.
Results: B7-H3 expression was detected in tumour/epithelial cells and immune cells, including macrophages, monocytes, dendritic cells (DCs) and myeloid-derived suppressor cells. B7-H3 was expressed at higher levels in cells within the tumour than in cells within non-neoplastic tissues. B7-H3 expression score in tumour cells positively correlated with the amount of CD45+ immune cells (rho = 0.305, P = 0.010), CD8+ T-cells (rho = 0.330, P = 0.005), and the percentage of CD8+/CD3+ T-cells (rho = 0.403, P < 0.001). Patients with high tumoural B7-H3 expression showed increased numbers of immune cells (P = 0.002), CD8+ T-cells (P = 0.011), natural killer cells (P = 0.073) and plasmacytoid DCs (P = 0.015). Tumoural B7-H3 expression was higher in males, smokers, squamous cell carcinomas, tumours with wild-type EGFR, poor differentiation, larger size and nodal metastasis (P < 0.05, all). Tumoural B7-H3 expression was associated with PD-L1 expression (P = 0.001), shorter 5-year overall survival (P = 0.012) and poor survival after anti-PD-1 blockade (P = 0.026).
Conclusions: Tumoural B7-H3 overexpression was associated with increased tumour-infiltrating cytotoxic lymphocytes and poor prognosis in NSCLC. Thus, B7-H3 is a promising prognostic biomarker and immunotherapeutic target in NSCLC.
Keywords: B7-H3; Immune checkpoint; Non–small-cell lung cancer; Tumour microenvironment; Tumour-infiltrating immune cells.
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