Identification And Clinical Significance Of B7-H3 Positive M2 Macrophages In Renal Cell Carcinoma Microenvironment

Objective:To analyze the expression of B7-H3~+M2 macrophages and its relationship with clinical pathologic features of patients with renal cell carcinoma.Methods:Part I:we collected paired tumor tissue and normal tissue of 39 patients who underwent radical nephrectomy due to renal cell carcinoma between 2015 and 2016 in the First Affiliated Hospital of Soochow University.We counted the patient's clinical data and postoperative pathology results and compared the expressions of B7-H3~+M2macrophages by flow cytometry.The association between the expression level and clinical pathologic parameters was analyzed through Chi-square test or Fisher exact test.we embedded the paired tumor tissue and normal tissue and examined the expression of B7-H3 and CD163 in serial sections of the tissues by immunohistochemistry.Then,location of the two molecule was assessed.Results:Part I:the expression level of B7-H3~+M2 macrophages in tumor tissues ranged from 16.7%to 52.3%(30.23%±7.59%),which was significantly higher than that in normal tissues(ranging from 2.6%to 27.5%,12.03±5.00%).We also found that there was a significant association between the expression level of B7-H3~+M2 macrophages and tumor grade(P=0.001),pT stage(P=0.001),positive lymph nodes(P=0.024),and distant metastases(P=0.017).However,no significant association was found between the expression level of B7-H3~+M2 macrophages and patients'age(P=0.508),sex(P=0.508),and tumor type(P=0.686).Part II:(1)B7-H3 expressed in both normal tissues and tumor tissues.In the normal renal tissues,renal tubules were positive staining for B7-H3 and the stroma were negative.However,it was positive staining extensively in tumor vasculature,tumor cells,and the stroma.(2)CD163 mainly expressed in interstitial regions which were enriched in blood vessels.(3)Co-expression of B7-H3 and CD163 was found in the tumor stroma surrounding vessels.Conclusions:CD163 expressed more in B7-H3~+monocytes in tumor tissues compared with normal tissues and B7-H3~+M2 monocytes mainly existed in tumor stroma which was enriched in vessels.High expression of CD163 in B7-H3~+monocytes indicates worse progression.