Expression of Fas Ligand by Human Gastric Adenocarcinomas: a Potential Mechanism of Immune Escape in Stomach Cancer

Overview

Journal Gut

Specialty Gastroenterology

Date 1999 Jan 23

PMID 9895372

Citations 39

Authors

M W Bennett

J OConnell

G C OSullivan

D Roche

C Brady

J Kelly

J K Collins

F Shanahan

Affiliations

Soon will be listed here.

Abstract

Background: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape.

Aim: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer.

Specimens: Thirty paraffin wax embedded human gastric adenocarcinomas.

Methods: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL).

Results: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour.

Conclusions: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.

Citing Articles

FGL1 Promotes Tumor Immune Escape in Stomach Adenocarcinoma via the Notch Signaling Pathway.

Zhou Y, Liu D, Li H Mol Biotechnol. 2023; 66(11):3203-3212.

PMID: 37902887 DOI: 10.1007/s12033-023-00928-3.

Secreted Fas Decoys Enhance the Antitumor Activity of Engineered and Bystander T Cells in Fas Ligand-Expressing Solid Tumors.

Bajgain P, Torres Chavez A, Balasubramanian K, Fleckenstein L, Lulla P, Heslop H Cancer Immunol Res. 2022; 10(11):1370-1385.

PMID: 36122411 PMC: 9633434. DOI: 10.1158/2326-6066.CIR-22-0115.

Cell death affecting the progression of gastric cancer.

Wang H, Liu M, Zeng X, Zheng Y, Wang Y, Zhou Y Cell Death Discov. 2022; 8(1):377.

PMID: 36038533 PMC: 9424204. DOI: 10.1038/s41420-022-01161-8.

Progesterone receptor gene serves as a prognostic biomarker associated with immune infiltration in gastric cancer: a bioinformatics analysis.

Li M, Zhou C Transl Cancer Res. 2022; 10(6):2663-2677.

PMID: 35116579 PMC: 8799212. DOI: 10.21037/tcr-21-218.

FasL PD-L2 Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease Progression.

Shan Z, Zhao Y, Zhang J, Yan Z, Wang T, Mao F Adv Sci (Weinh). 2021; 9(5):e2103543.

PMID: 34957697 PMC: 8844550. DOI: 10.1002/advs.202103543.

References

Rayner A, Grimm E, Lotze M, Chu E, Rosenberg S . Lymphokine-activated killer (LAK) cells. Analysis of factors relevant to the immunotherapy of human cancer. Cancer. 1985; 55(6):1327-33. DOI: 10.1002/1097-0142(19850315)55:6<1327::aid-cncr2820550628>3.0.co;2-o. View

Griffith T, Brunner T, Fletcher S, Green D, Ferguson T . Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995; 270(5239):1189-92. DOI: 10.1126/science.270.5239.1189. View

Daniel P, Krammer P . Activation induces sensitivity toward APO-1 (CD95)-mediated apoptosis in human B cells. J Immunol. 1994; 152(12):5624-32. View

Mountz J, Zhou T, Bluethmann H, Wu J, Edwards 3rd C . Apoptosis defects analyzed in TcR transgenic and fas transgenic lpr mice. Int Rev Immunol. 1994; 11(4):321-42. DOI: 10.3109/08830189409051178. View

Alderson M, Tough T, Braddy S, Falk B, Schooley K, Goodwin R . Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med. 1995; 181(1):71-7. PMC: 2191813. DOI: 10.1084/jem.181.1.71. View

Nagata S, Golstein P . The Fas death factor. Science. 1995; 267(5203):1449-56. DOI: 10.1126/science.7533326. View

Tanaka M, Suda T, Takahashi T, Nagata S . Expression of the functional soluble form of human fas ligand in activated lymphocytes. EMBO J. 1995; 14(6):1129-35. PMC: 398190. DOI: 10.1002/j.1460-2075.1995.tb07096.x. View

Inoue H, Mori M, Honda M, Li J, Shibuta K, Mimori K . The expression of tumor-rejection antigen "MAGE" genes in human gastric carcinoma. Gastroenterology. 1995; 109(5):1522-5. DOI: 10.1016/0016-5085(95)90639-8. View

Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke R . A role for CD95 ligand in preventing graft rejection. Nature. 1995; 377(6550):630-2. DOI: 10.1038/377630a0. View

10.

Galle P, Hofmann W, Walczak H, Schaller H, Otto G, Stremmel W . Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. J Exp Med. 1995; 182(5):1223-30. PMC: 2192196. DOI: 10.1084/jem.182.5.1223. View

11.

Eischen C, Schilling J, Lynch D, Krammer P, Leibson P . Fc receptor-induced expression of Fas ligand on activated NK cells facilitates cell-mediated cytotoxicity and subsequent autocrine NK cell apoptosis. J Immunol. 1996; 156(8):2693-9. View

12.

Lau H, Yu M, Fontana A, Stoeckert Jr C . Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. Science. 1996; 273(5271):109-12. DOI: 10.1126/science.273.5271.109. View

13.

Liles W, Kiener P, Ledbetter J, Aruffo A, Klebanoff S . Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: implications for the regulation of apoptosis in neutrophils. J Exp Med. 1996; 184(2):429-40. PMC: 2192712. DOI: 10.1084/jem.184.2.429. View

14.

Hahne M, Rimoldi D, Schroter M, Romero P, Schreier M, French L . Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science. 1996; 274(5291):1363-6. DOI: 10.1126/science.274.5291.1363. View

15.

Strand S, Hofmann W, Hug H, Muller M, Otto G, Strand D . Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion?. Nat Med. 1996; 2(12):1361-6. DOI: 10.1038/nm1296-1361. View

16.

Korbutt G, Elliott J, Rajotte R . Cotransplantation of allogeneic islets with allogeneic testicular cell aggregates allows long-term graft survival without systemic immunosuppression. Diabetes. 1997; 46(2):317-22. DOI: 10.2337/diab.46.2.317. View

17.

Seino K, Kayagaki N, Okumura K, Yagita H . Antitumor effect of locally produced CD95 ligand. Nat Med. 1997; 3(2):165-70. DOI: 10.1038/nm0297-165. View

18.

Stuart P, Griffith T, Usui N, Pepose J, Yu X, Ferguson T . CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival. J Clin Invest. 1997; 99(3):396-402. PMC: 507812. DOI: 10.1172/JCI119173. View

19.

OConnell J, OSullivan G, Collins J, Shanahan F . The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med. 1996; 184(3):1075-82. PMC: 2192789. DOI: 10.1084/jem.184.3.1075. View

20.

Niehans G, Brunner T, Frizelle S, Liston J, Salerno C, Knapp D . Human lung carcinomas express Fas ligand. Cancer Res. 1997; 57(6):1007-12. View