Geerdes Emma E, Sideras Kostandinos, Aziz M Hosein, van Eijck Casper H, Bruno Marco J, Sprengers Dave, Boor Patrick P C, Kwekkeboom Jaap
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands.
Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, Netherlands.
Front Oncol. 2021 Apr 29;11:615691. doi: 10.3389/fonc.2021.615691. eCollection 2021.
B7-H3 is an immunomodulatory member of the B7-superfamily with limited expression in normal tissues, but overexpression in several types of cancer. Therefore it is currently being explored as a potential target for cancer immunotherapy. The biological relevance of B7-H3 expression in pancreatic cancer is unclear, while there are no data on B7-H3 expression in ampullary cancer. We aimed to compare intra-tumoral B7-H3 expression between these two closely related cancer types and analyze its association with post-surgical disease course. B7-H3 expression levels were determined by immunohistochemistry in tissue microarrays of resected tumors of 137 pancreatic cancer patients and 83 patients with ampullary cancer of the pancreato-biliary subtype. B7-H3 was more frequently expressed in cancer cells of ampullary cancer patients compared to pancreatic cancer patients (51% 21%; p< 0.001). In ampullary cancer patients, but not in pancreatic cancer patients, B7-H3 cancer cell expression was associated with longer disease-free survival and patient survival. However, the prognostic value of B7-H3 was lost upon adjustment for CA19-9 levels. The frequencies of B7-H3 expression in tumor stroma did not differ between the two types of cancer (66% versus 63%). In both cancer types, stromal B7-H3 expression was not associated with post-surgical disease course. Compared to pancreatic cancer, B7-H3 is more frequently expressed in cancer cells of patients with the pancreato-biliary subtype of ampullary cancer. These data suggest that B7-H3 may represent an interesting potential target for immunotherapy in ampullary cancer rather than in pancreatic cancer.
B7-H3是B7超家族的免疫调节成员，在正常组织中表达有限，但在多种癌症类型中过表达。因此，它目前正作为癌症免疫治疗的潜在靶点进行研究。B7-H3在胰腺癌中表达的生物学相关性尚不清楚，而关于壶腹癌中B7-H3表达的数据也未见报道。我们旨在比较这两种密切相关癌症类型之间肿瘤内B7-H3的表达情况，并分析其与手术后疾病进程的关联。通过免疫组织化学法测定了137例胰腺癌患者和83例胰胆管亚型壶腹癌患者切除肿瘤的组织微阵列中B7-H3的表达水平。与胰腺癌患者相比，壶腹癌患者的癌细胞中B7-H3表达更为频繁（51%对21%；p<0.001）。在壶腹癌患者中，而非胰腺癌患者中，B7-H3癌细胞表达与更长的无病生存期和患者生存期相关。然而，在调整CA19-9水平后，B7-H3的预后价值丧失。两种癌症类型之间肿瘤基质中B7-H3表达的频率没有差异（66%对63%）。在两种癌症类型中，基质B7-H3表达均与手术后疾病进程无关。与胰腺癌相比，B7-H3在胰胆管亚型壶腹癌患者的癌细胞中表达更为频繁。这些数据表明，B7-H3可能是壶腹癌而非胰腺癌免疫治疗中一个有意义的潜在靶点。
