Clinical Importance of B7-H3 Expression in Human Pancreatic Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2009 Oct 22

PMID 19844235

Citations 94

Authors

I Yamato

M Sho

T Nomi

T Akahori

K Shimada

K Hotta

H Kanehiro

N Konishi

H Yagita

Y Nakajima

Affiliations

Soon will be listed here.

Abstract

Background: B7-H3 is a new member of the B7 ligand family and regulates T-cell responses in various conditions. However, the role of B7-H3 in tumour immunity is largely unknown. The purpose of this study was to evaluate the clinical significance of B7-H3 expression in human pancreatic cancer and the therapeutic potential for cancer immunotherapy.

Methods: We investigated B7-H3 expression in 59 patients with pancreatic cancer by immunohistochemistry and real-time PCR. Furthermore, we examined the anti-tumour effect of B7-H3-blocking monoclonal antibody in vivo in a murine pancreatic cancer model.

Results: Tumour-related B7-H3 expression was abundant in most human pancreatic cancer tissues and was significantly higher compared with that in non-cancer tissue or normal pancreas. Moreover, its expression was significantly more intense in cases with lymph node metastasis and advanced pathological stage. B7-H3 blockade promoted CD8(+) T-cell infiltration into the tumour and induced a substantial anti-tumour effect on murine pancreatic cancer. In addition, the combination of gemcitabine with B7-H3 blockade showed a synergistic anti-tumour effect without overt toxicity.

Conclusion: Our data show for the first time that B7-H3 may have a critical role in pancreatic cancer and provide the rationale for developing a novel cancer immunotherapy against this fatal disease.

Citing Articles

UBE2T/CDC42/CD276 signaling axis mediates brain metastasis of triple-negative breast cancer via lysosomal autophagy.

Shi L, Chen Y, Xie M, Chen Q, Qiao X, Cheng Q J Immunother Cancer. 2025; 13(2).

PMID: 39915000 PMC: 11804199. DOI: 10.1136/jitc-2024-010782.

B7 homolog 3 in pancreatic cancer.

Perovic D, Dusanovic Pjevic M, Perovic V, Grk M, Rasic M, Milickovic M World J Gastroenterol. 2024; 30(31):3654-3667.

PMID: 39193002 PMC: 11346158. DOI: 10.3748/wjg.v30.i31.3654.

CD276 Promotes an Inhibitory Tumor Microenvironment in Hepatocellular Carcinoma and is Associated with Poor Prognosis.

Liu W, Jiang Q, Qi Z, Zhang F, Tang W, Wang H J Hepatocell Carcinoma. 2024; 11:1357-1373.

PMID: 39011124 PMC: 11247130. DOI: 10.2147/JHC.S469529.

Rapidly-manufactured CD276 CAR-T cells exhibit enhanced persistence and efficacy in pancreatic cancer.

Deng T, Deng Y, Tsao S, Xiong Q, Yao Y, Liu C J Transl Med. 2024; 22(1):633.

PMID: 38978106 PMC: 11229349. DOI: 10.1186/s12967-024-05462-7.

CAR T cells redirected to B7-H3 for pediatric solid tumors: Current status and future perspectives.

Epperly R, Gottschalk S, DeRenzo C EJC Paediatr Oncol. 2024; 3.

PMID: 38957786 PMC: 11218663. DOI: 10.1016/j.ejcped.2024.100160.

References

Hodi F, Butler M, Oble D, Seiden M, Haluska F, Kruse A . Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A. 2008; 105(8):3005-10. PMC: 2268575. DOI: 10.1073/pnas.0712237105. View

Sun M, Richards S, Prasad D, Mai X, Rudensky A, Dong C . Characterization of mouse and human B7-H3 genes. J Immunol. 2002; 168(12):6294-7. DOI: 10.4049/jimmunol.168.12.6294. View

Luo L, Qiao H, Meng F, Dong X, Zhou B, Jiang H . Arsenic trioxide synergizes with B7H3-mediated immunotherapy to eradicate hepatocellular carcinomas. Int J Cancer. 2005; 118(7):1823-30. DOI: 10.1002/ijc.21557. View

Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H . Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res. 2007; 13(7):2151-7. DOI: 10.1158/1078-0432.CCR-06-2746. View

Laheru D, Jaffee E . Immunotherapy for pancreatic cancer - science driving clinical progress. Nat Rev Cancer. 2005; 5(6):459-67. DOI: 10.1038/nrc1630. View

Wang L, Fraser C, Kikly K, Wells A, Han R, Coyle A . B7-H3 promotes acute and chronic allograft rejection. Eur J Immunol. 2005; 35(2):428-38. DOI: 10.1002/eji.200425518. View

Plate J . Current immunotherapeutic strategies in pancreatic cancer. Surg Oncol Clin N Am. 2007; 16(4):919-43, xi. DOI: 10.1016/j.soc.2007.07.012. View

Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N . Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res. 2005; 11(8):2947-53. DOI: 10.1158/1078-0432.CCR-04-1469. View

Li D, Xie K, Wolff R, Abbruzzese J . Pancreatic cancer. Lancet. 2004; 363(9414):1049-57. DOI: 10.1016/S0140-6736(04)15841-8. View

10.

Yi K, Chen L . Fine tuning the immune response through B7-H3 and B7-H4. Immunol Rev. 2009; 229(1):145-51. PMC: 2696224. DOI: 10.1111/j.1600-065X.2009.00768.x. View

11.

Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K . Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007; 297(3):267-77. DOI: 10.1001/jama.297.3.267. View

12.

Sho M, Yamada A, Najafian N, Salama A, Harada H, Sandner S . Physiological mechanisms of regulating alloimmunity: cytokines, CTLA-4, CD25+ cells, and the alloreactive T cell clone size. J Immunol. 2002; 169(7):3744-51. DOI: 10.4049/jimmunol.169.7.3744. View

13.

Chapoval A, Ni J, Lau J, Wilcox R, Flies D, Liu D . B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol. 2001; 2(3):269-74. DOI: 10.1038/85339. View

14.

Zhang G, Zhou H, Chen Y, Ge Y, Xie F, Shi Q . Characterization and application of two novel monoclonal antibodies against 2IgB7-H3: expression analysis of 2IgB7-H3 on dendritic cells and tumor cells. Tissue Antigens. 2005; 66(2):83-92. DOI: 10.1111/j.1399-0039.2005.00449.x. View

15.

Suzuki E, Kapoor V, Jassar A, Kaiser L, Albelda S . Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005; 11(18):6713-21. DOI: 10.1158/1078-0432.CCR-05-0883. View

16.

Lupu C, Eisenbach C, Lupu A, Kuefner M, Hoyler B, Stremmel W . Adenoviral B7-H3 therapy induces tumor specific immune responses and reduces secondary metastasis in a murine model of colon cancer. Oncol Rep. 2007; 18(3):745-8. View

17.

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

18.

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

19.

Sun X, Vale M, Leung E, Kanwar J, Gupta R, Krissansen G . Mouse B7-H3 induces antitumor immunity. Gene Ther. 2003; 10(20):1728-34. DOI: 10.1038/sj.gt.3302070. View

20.

Traverso L . Pancreatic cancer: surgery alone is not sufficient. Surg Endosc. 2006; 20 Suppl 2:S446-9. DOI: 10.1007/s00464-006-0052-1. View