Effects of B7-H3 expression on tumour-infiltrating immune cells and clinicopathological characteristics in non-small-cell lung cancer.

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). 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. 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). 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.

Yim J ，Koh J ，Kim S ，Song SG ，Ahn HK ，Kim YA ，Jeon YK ，Chung DH ... -  《-》

Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC).

Carvajal-Hausdorf D ，Altan M ，Velcheti V ，Gettinger SN ，Herbst RS ，Rimm DL ，Schalper KA ... -  《Journal for ImmunoTherapy of Cancer》

B7-H1 and B7-H3 are independent predictors of poor prognosis in patients with non-small cell lung cancer.

Mao Y ，Li W ，Chen K ，Xie Y ，Liu Q ，Yao M ，Duan W ，Zhou X ，Liang R ，Tao M ... -  《Oncotarget》

B7-H3 in combination with regulatory T cell is associated with tumor progression in primary human non-small cell lung cancer.

Jin Y ，Zhang P ，Li J ，Zhao J ，Liu C ，Yang F ，Yang D ，Gao A ，Lin W ，Ma X ，Sun Y ... -  《International Journal of Clinical and Experimental Pathology》

B7-H3 Expression in NSCLC and Its Association with B7-H4, PD-L1 and Tumor-Infiltrating Lymphocytes.

Purpose: The immune checkpoint PD-1 and its receptor B7-H1 (PD-L1) are successful therapeutic targets in cancer but less is known about other B7 family members. Here, we determined the expression level of B7-H3 protein in non-small cell lung cancer (NSCLC) and evaluated its association with tumor-infiltrating lymphocytes (TIL), PD-L1, B7-H4, and major clinicopathologic characteristics is in 3 NSCLC cohorts.Experimental design: We used multiplexed automated quantitative immunofluorescence (QIF) to assess the levels of B7-H3, PD-L1, B7-H4, and TILs in 634 NSCLC cases with validated antibodies. Associations between the marker levels, major clinicopathologic variables and survival were analyzed.Results: Expression of B7-H3 protein was found in 80.4% (510/634) of the cases. High B7-H3 protein level (top 10 percentile) was associated with poor overall survival (P < 0.05). Elevated B7-H3 was consistently associated with smoking history across the 3 cohorts, but not with sex, age, clinical stage, and histology. Coexpression of B7-H3 and PD-L1 was found in 17.6% of the cases (112/634) and with B7-H4 in 10% (63/634). B7-H4 and PD-L1 were simultaneously detected only in 1.8% of NSCLCs (12/634). The expression of B7-H3 was not associated with the levels of CD3-, CD8-, and CD20-positive TILs.Conclusions: B7-H3 protein is expressed in the majority of NSCLCs and is associated with smoking history. High levels of B7-H3 protein have a negative prognostic impact in lung carcinomas. Coexpression of B7-H3 with PD-L1 and B7-H4 is relatively low, suggesting a nonredundant biological role of these targets. Clin Cancer Res; 23(17); 5202-9. ©2017 AACR.

Altan M ，Pelekanou V ，Schalper KA ，Toki M ，Gaule P ，Syrigos K ，Herbst RS ，Rimm DL ... -  《-》