Abstract
BackgroundIn recent years, immune checkpoint inhibitors have shown significant effects in a variety of solid tumors. However, due to the low incidence of small cell lung cancer (SCLC) and its unclear mechanism, immune checkpoints in SCLC have not been fully studied.MethodsWe evaluated the expression of PD-L1, B7-H3, and B7-H4 in 115 SCLC tissue specimens using immunohistochemistry. The clinical data of patients with SCLC were retrospectively reviewed to investigate three negative co-stimulatory B7 family molecules’ ability to affect the prognosis of SCLC.ResultsAmong the SCLC patients with complete follow-up data (n = 107), sixty-nine (64.49%) expressed moderate to high B7-H3 levels, which correlated positively with tumor sizes (P < 0.001). Eighty (74.77%) patients expressed moderate to high B7-H4 levels, which correlated positively with metastases (P = 0.049). The positive expression of B7-H3 and B7-H4 correlated significantly with shortened overall survival (OS) (B7-H3, P = 0.006; B7-H4, P = 0.019). PD-L1 was positively expressed only in 13.08% of cancer tissues, and there was no significant correlation with prognosis. The Cox proportional hazards regression showed that B7-H3 was an independent prognostic indicator of OS (P = 0.028; HR = 2.125 [95% CI = 0.985-4.462]).ConclusionsOur results suggest that B7-H3 has a negative predictive effect on SCLC. This outcome provides a theoretical basis for the subsequent research on immune checkpoint inhibitors targeting B7-H3.
Highlights
With changes in the living environment and lifestyle, malignant tumors have become the leading cause of death for most people in the world [1]
The immunohistochemical staining of PD-L1, B7-H3, and B7H4 for the Tissue microarrays (TMAs) of 115 small cell lung cancer patients and their adjacent tissues was performed, of which 1 pair of the immunohistochemical images were absent from B7-H3, and 3 pairs were absent from B7-H4
The results showed that the B7-H4 protein expression was not an independent prognostic factor of OS (Hazard ratio = 1.789; 95% confidence interval (CI): 0.933-3.256; P = 0.251)
Summary
With changes in the living environment and lifestyle, malignant tumors have become the leading cause of death for most people in the world [1]. Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death. Small cell lung cancer (SCLC) accounts for about 15% of lung cancers, has a high degree of malignancy, and is highly invasive [2]. Early SCLC is relatively sensitive to chemoradiotherapy, only a small proportion of patients achieve complete remission. Immune checkpoint inhibitors have shown significant effects in a variety of solid tumors. Due to the low incidence of small cell lung cancer (SCLC) and its unclear mechanism, immune checkpoints in SCLC have not been fully studied
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