Original CommunicationsPancreatic cancer cells can evade immune surveillance via nonfunctional Fas (APO-1/CD95) receptors and aberrant expression of functional Fas ligand☆,☆☆
Section snippets
Cell lines and pancreatic cancer tissue collection
MPanc-9621 and BW-1 are human pancreatic cancer cell lines derived from surgical specimens obtained with institutional review board approval. Normal pancreatic and confirmed pancreatic cancer specimens were supplied by Dr R. Odze (Department of Pathology, Brigham and Women's Hospital, Boston, Mass). Pancreatic cancer cell lines AsPc-1, BxPc-3, Capan-1, Capan-2, CFPAC-1, Colo-587, HPAF-2, Hs700T, Hs766T, MiaPaCa-2, Panc-1, Su86.86, mouse embryo fibroblast cell line 3T6 (Swiss albino), the Daudi
FasR is expressed in pancreatic cancer
All 14 pancreatic cancer cell lines expressed FasR as detected by flow cytometry (Fig 1, a , Table I).
Discussion
The data shown in this study suggest that pancreatic cancer cells may use 2 mechanisms of evading Fas-mediated immune surveillance. First, pancreatic cancer cells may resist Fas-mediated apoptosis by expressing a nonfunctional FasR. Second, most, if not all, pancreatic cancer cells aberrantly express functional FasL and can induce apoptosis in Fas-sensitive activated T-cells.
Other reports have shown a down-regulation or loss of FasR expression in human breast cancer cell lines,26 hepatoma cell
References (44)
- et al.
Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4
Cell
(1992) Inhibition of human NK cell and LAK cell cytotoxicity and differentiation by PGE2
Cell Immunol
(1989)Apoptosis by death factor
Cell
(1997)- et al.
Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family
Cell
(1993) - et al.
Quantification of apoptotic events in pure and heterogeneous populations of cells using the flow cytometer
Methods Cell Biol
(1995) - et al.
The role of FasL-induced apoptosis in immune privilege
Immunol Today
(1997) - et al.
National patterns of care for pancreatic cancer
Ann Surg
(1996) - et al.
p53 and K-ras alterations in pancreatic epithelial cell lesions
Oncogene
(1993) - et al.
Tumor heterogeneity and immunotherapy of cancer
Immunol Rev
(1995) - et al.
Expression of HLA-A,B,C antigens on primary and metastatic tumor cell populations of human carcinomas
Cancer Res
(1991)
Identification of human cancers deficient in antigen processing
J Exp Med
ICAM- melanoma cells are relatively resistant to CD3-mediated T-cell lysis
Int J Cancer
Anti-transforming growth factor (TGF)-β antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity
J Clin Invest
Deacetylase10 activity of human tumor cells producing immunosuppressive aminosugars: its possible role in resistance to cell-mediated cytotoxicity
Cancer Res
Breast cancer-associated antigen, DF3/MUC1, induces apoptosis of activated human T cells
Nat Med
An immune suppressive factor derived from esophageal squamous carcinoma induces apoptosis in normal and transformed cells of lymphoid lineage
J Immunol
Perforin, Fas ligand, and tumor necrosis factor are the major cytotoxic molecules used by lymphokine-activated killer cells
J Immunol
Monoclonal antibody-mediated tumor regression by induction of apoptosis
Science
Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity
Science
A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice
J Exp Med
Role of Fas ligand (CD95L) in immune escape: the tumor cell strikes back
J Immunol
Lack of evidence for expression of Fas ligand in Fas-bearing tumors
Oncol Rep
Cited by (105)
The footprint of kynurenine pathway in every cancer: a new target for chemotherapy
2021, European Journal of PharmacologyCitation Excerpt :Likewise, cancer cells can develop particular mechanisms to counteract immune cells. For instance, FAS ligand is significantly expressed in cancer cells and transfers death signal to effector T cells (Bernstorff et al., 1999). Regarding this point of view, new generations of chemotherapy agents are developing to improve immune function and counteract immune evasion mechanisms of cancers.
Immunotherapy in pancreatic ductal adenocarcinoma: An emerging entity?
2017, Annals of OncologyCXCR5<sup>+</sup> CD8<sup>+</sup> T cells potently infiltrate pancreatic tumors and present high functionality
2017, Experimental Cell ResearchCitation Excerpt :The immunosuppressive cytokines IL-10 and TGF-s are secreted by pancreatic tumor cells and mediate immune suppression [11,12]. Furthermore, pancreatic tumor cells also interfere with Fas-mediated cell death by expressing non-functional Fas receptor and upregulate Fas ligand to mediate the elimination of other Fas-susceptible cells [13]. In addition, a immune checkpoint molecule PD-L1, which signals to PD-1 and mediates T cell exhaustion and cell death, is expressed by myeloid derived suppressor cells associated with pancreatic tumors and is capable to suppressing effector T cell function [14].
Targeting tumor tolerance: A new hope for pancreatic cancer therapy?
2016, Pharmacology and TherapeuticsHigh Fas expression in gastric carcinoma cells as a factor correlating with the occurrence of metastases to regional lymph nodes
2014, Advances in Medical SciencesCitation Excerpt :Disturbances of the membrane apoptosis pathway, which includes Fas and Fas-L proteins, are critical in the formation of numerous neoplasms of the digestive tract. They are described as factors which can influence formation and development of colorectal carcinoma [14–18] and pancreas carcinoma [19–21]. This group also comprises gastric carcinoma which is one of the most common neoplasms of the digestive tract and is characterized by poor prognosis.
- ☆
Supported by a grant from Dr Mildred Scheel Stiftung für Krebsforschung D/96/17181 (W.v.B.) and in part by National Institutes of Health grant T32CA09535 and National Institutes of Health R01 grants CA 45854 and CA 606662.
- ☆☆
Reprint requests: Timothy J. Eberlein, MD, Bixby Professor and Chairman, Department of Surgery, Washington University School of Medicine, 660 S Euclid Ave, Box 8109, St Louis, MO 63110.