Association of Increased B7 Protein Expression by Infiltrating Immune Cells with Progression of Gastric Carcinogenesis

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2019 Mar 1

PMID 30813210

Citations 14

Authors

Lingchuan Guo

Zhiju Liu

Yun Zhang

Qiuying Quan

Lili Huang

Yunyun Xu

Lei Cao

Xueguang Zhang

Affiliations

Soon will be listed here.

Abstract

B7 negative costimulatory molecules are a group of molecules associated with the occurrence, development, and therapy of cancers. Here, we aimed to determine the clinical significance of PD-L1, B7-H3, and B7-H4 and their expression in CD8 and CD68 positive cells at different stages of gastric carcinogenesis.We detected PD-L1, B7-H3, B7-H4, CD8, and CD68 expression in samples by immunohistochemical staining of 62 chronic superficial gastritis (CSG) samples, 72 chronic atrophic gastritis (CAG) samples, 68 low-grade intraepithelial neoplasia (LIN) samples, 65 high-grade intraepithelial neoplasia (HIN) samples obtained from gastroscopic biopsies and 50 gastric adenocarcinoma (GA) samples obtained from surgical resections. Then we statistically analyzed the expression differences and correlations.Our results indicated that B7 and CD68 expression on infiltrating immune cells was associated with disease progression. However, infiltration of CD8+ cells decreased with disease progression. B7-H3 expression was markedly enhanced at neoplasia and GA stages. B7-H3 in tumor cells was negatively correlated with CD8-expressing cells. Conversely, B7-H3 expression in tumor-infiltrating immune cells was positively correlated with CD68-expressing cells. B7-H4 expression was found in the cell membrane at the stages of gastritis and low-grade neoplasia and was gradually expressed in the cytoplasm at high-grade neoplasia and GA stages. High B7-H4 expression in infiltrating immune cells was also significantly associated with lower CD8-positive and higher CD68-positive cell densities.Increased B7 protein expression by infiltrating immune cells was associated with disease progression, and specifically, the level of B7-H3 expression and localization of B7-H4 expression differed significantly among different stages of gastric carcinogenesis.

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References

Freeman G, Long A, Iwai Y, Bourque K, Chernova T, Nishimura H . Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000; 192(7):1027-34. PMC: 2193311. DOI: 10.1084/jem.192.7.1027. View

Tajiri H, Doi T, Endo H, Nishina T, Terao T, Hyodo I . Routine endoscopy using a magnifying endoscope for gastric cancer diagnosis. Endoscopy. 2002; 34(10):772-7. DOI: 10.1055/s-2002-34267. View

Ozkaynak E, Wang L, Goodearl A, McDonald K, Qin S, OKeefe T . Programmed death-1 targeting can promote allograft survival. J Immunol. 2002; 169(11):6546-53. DOI: 10.4049/jimmunol.169.11.6546. View

Curiel T, Wei S, Dong H, Alvarez X, Cheng P, Mottram P . Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med. 2003; 9(5):562-7. DOI: 10.1038/nm863. View

Choi I, Zhu G, Sica G, Strome S, Cheville J, Lau J . Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol. 2003; 171(9):4650-4. DOI: 10.4049/jimmunol.171.9.4650. View

Ohno S, Inagawa H, Dhar D, Fujii T, Ueda S, Tachibana M . The degree of macrophage infiltration into the cancer cell nest is a significant predictor of survival in gastric cancer patients. Anticancer Res. 2004; 23(6D):5015-22. View

Chen L . Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol. 2004; 4(5):336-47. DOI: 10.1038/nri1349. View

Henson D, Dittus C, Younes M, Nguyen H, Albores-Saavedra J . Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973-2000: increase in the signet ring cell type. Arch Pathol Lab Med. 2004; 128(7):765-70. DOI: 10.5858/2004-128-765-DTITIA. View

Wu C, Jiang J, Tan M, Zhu Y, Ji M, Xu K . Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis. World J Gastroenterol. 2006; 12(3):457-9. PMC: 4066068. DOI: 10.3748/wjg.v12.i3.457. View

10.

Das S, Suarez G, Beswick E, Sierra J, Graham D, Reyes V . Expression of B7-H1 on gastric epithelial cells: its potential role in regulating T cells during Helicobacter pylori infection. J Immunol. 2006; 176(5):3000-9. DOI: 10.4049/jimmunol.176.5.3000. View

11.

Zou W, Chen L . Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008; 8(6):467-77. DOI: 10.1038/nri2326. View

12.

Seliger B, Marincola F, Ferrone S, Abken H . The complex role of B7 molecules in tumor immunology. Trends Mol Med. 2008; 14(12):550-9. PMC: 2726789. DOI: 10.1016/j.molmed.2008.09.010. View

13.

Fitzgerald R, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V . Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010; 47(7):436-44. PMC: 2991043. DOI: 10.1136/jmg.2009.074237. View

14.

Wu Y, Lin C, Cheng K, Lin C, Wang Y, Lin I . Increased programmed death-ligand-1 expression in human gastric epithelial cells in Helicobacter pylori infection. Clin Exp Immunol. 2010; 161(3):551-9. PMC: 2962974. DOI: 10.1111/j.1365-2249.2010.04217.x. View

15.

Zhang G, Wang J, Kelly J, Gu G, Hou J, Zhou Y . B7-H3 augments the inflammatory response and is associated with human sepsis. J Immunol. 2010; 185(6):3677-84. DOI: 10.4049/jimmunol.0904020. View

16.

Wang B, Xu D, Yu X, Ding T, Rao H, Zhan Y . Association of intra-tumoral infiltrating macrophages and regulatory T cells is an independent prognostic factor in gastric cancer after radical resection. Ann Surg Oncol. 2011; 18(9):2585-93. DOI: 10.1245/s10434-011-1609-3. View

17.

Correa P, Fox J, Fontham E, Ruiz B, Lin Y, Zavala D . Helicobacter pylori and gastric carcinoma. Serum antibody prevalence in populations with contrasting cancer risks. Cancer. 1990; 66(12):2569-74. DOI: 10.1002/1097-0142(19901215)66:12<2569::aid-cncr2820661220>3.0.co;2-i. View

18.

Kou Y, Koag M, Cheun Y, Shin A, Lee S . Application of hypoiodite-mediated aminyl radical cyclization to synthesis of solasodine acetate. Steroids. 2012; 77(11):1069-74. DOI: 10.1016/j.steroids.2012.05.002. View

19.

Kou Y, Cheun Y, Koag M, Lee S . Synthesis of 14',15'-dehydro-ritterazine Y via reductive and oxidative functionalizations of hecogenin acetate. Steroids. 2012; 78(2):304-11. DOI: 10.1016/j.steroids.2012.10.021. View

20.

Zhang L, Wu H, Lu D, Li G, Sun C, Song H . The costimulatory molecule B7-H4 promote tumor progression and cell proliferation through translocating into nucleus. Oncogene. 2013; 32(46):5347-58. PMC: 3898118. DOI: 10.1038/onc.2012.600. View