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

BACKGROUND: Small cell lung cancer (SCLC) accounts for 10–15% of all lung malignancies and its prognosis is dismal. Although early studies have shown promising clinical activity of immune checkpoint blockers, the immune composition and expression of potentially actionable immunostimulatory targets in this malignancy are poorly understood. METHODS: Using multiplexed quantitative immunofluorescence (QIF), we measured the levels of 3 different B7 family ligands PD-L1, B7-H3, B7-H4 and major tumor infiltrating lymphocyte (TIL) subsets in 90 SCLC samples represented in tissue microarray format. Associations between the marker levels, clinicopathological variables and survival were studied. RESULTS: PD-L1 protein was detected in 7.3%, B7-H3 in 64.9% and B7-H4 in 2.6% of SCLC cases. The markers showed limited co-expression and were not associated with the level of TILs, age, gender and stage. Elevated B7-H4 was associated with shorter 5-year overall survival. The levels of CD3+, CD8+ and CD20+ TILs and the ratio of total/effector T-cells were significantly lower in SCLC than in non-small cell lung cancer. High levels of CD3+, but not CD8+ or CD20+ TILs were significantly associated with longer survival. CONCLUSIONS: Taken together, our study indicate variable expression and clinical role of B7-family ligands in SCLC with predominant expression of the candidate target B7-H3 and the presence of a limited cytotoxic anti-tumor immune response. These results support the evaluation of B7-H3 blockers and/or pro-inflammatory therapies in SCLC.