Abstract

B7-H3 (CD276), a member of the family of immune modulators, orchestrates antitumor immunity. To date, only small-sized studies have examined the association of B7-H3 expression with survival in pancreatic cancer, yielding inconclusive results. We evaluated tumor B7-H3 expression in 150 consecutive patients with pancreatic ductal adenocarcinoma using immunohistochemistry. B7-H3 expression was positive (≥10% tumor cells) in 99 of 150 (66%) cases of pancreatic cancer. We classified the tumors into four groups depending on B7-H3 expression (negative, low, intermediate, and high) and found that higher B7-H3 expression was independently associated with lower disease-free survival (DFS; for high vs. negative B7-H3 expression: multivariable hazard ratio (HR) = 3.12; 95% confidence interval (CI) = 1.48–6.15; Ptrend = 0.0026). Furthermore, the association of B7-H3 expression with survival differed according to the pathological stage (p-stage) (Pinteraction = 0.048, between p-stages I–II and III–IV). The association of B7-H3 positivity with lower DFS was stronger in tumors with p-stage I–II (multivariable HR = 3.10, 95% CI = 1.75–5.69; P < 0.0001) than in those with p-stage III–IV (multivariable HR = 1.20, 95% CI = 0.67–2.28; P = 0.55). We demonstrated that tumor high B7-H3 expression is independently associated with poor survival in patients with pancreatic cancer and that this association is stronger in tumors with p-stage I–II than in those with p-stage III–IV. B7-H3 expression may be a useful prognostic biomarker for identifying aggressive early-stage pancreatic cancer.

Highlights

  • Pancreatic cancer is one of the most life-threatening malignancies, with the highest mortality among all solid tumors [1,2]

  • Recent evidence demonstrates that B7-H3 blockade, especially when combined with an anti-PD-1 blockade, is a promising strategy for the treatment of B7-H3-expressing non-small-cell lung cancer (NSCLC) that are refractory to anti-PD-1 therapy [22], making B7-H3 a promising molecular target [22,23,24,25,26,27,28]

  • We examined whether the association of B7-H3 expression with patient mortality differed according to clinicopathological variables

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Summary

Introduction

Pancreatic cancer is one of the most life-threatening malignancies, with the highest mortality among all solid tumors [1,2] It is characterized by an abundant stromal component that comprises up to 90% of its total volume [2,3,4,5,6,7,8,9,10]. Emerging immunotherapies, including anti-PD-1 (PDCD1)/PD-L1 (CD274) antibodies, have been used effectively to treat several types of cancers, including non-small-cell lung cancer (NSCLC) and malignant melanoma [11,12]; these therapies lack efficacy in treating pancreatic cancers, partly due to their abundant stroma with an immunosuppressive microenvironment [2,3,4,5,6,7,8,9,10,13,14,15,16,17,18]. No study has examined whether the association of B7-H3 expression with survival differs according to clinicopathological variables in pancreatic cancer

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