Role of Fas ligand expression in promoting escape from immune rejection in a spontaneous tumor model.
Tumors escape immune-mediated rejection by a variety of mechanisms during tumor progression. The elucidation of these mechanisms in vivo suffers from a lack of suitable models of spontaneous tumor formation escaping active specific immunotherapy (ASI). In a rat neu transgenic (rNeu-TG) mouse model of spontaneous breast tumor formation, we showed that rNeu-TG mice developed late escape tumors despite the presence of a persistent rNeu-specific immune response after ASI. Cell suspensions derived from these escape tumors grew in vaccinated tumor-free mice, whereas injected spontaneous tumor cells were rejected. Escape tumors retained rNeu or MHC class I expression but significantly upregulated Fas (CD95, Apo-1) ligand. We further demonstrated that Fas-L on escape tumor cells correlated with apoptosis of infiltrating T lymphocytes. Thus, our results provide evidence that spontaneous breast tumors upregulate Fas-L expression after vaccination that may promote tumor escape in vivo after ASI.
Céfai
D
D
Department of Clinical Research, University of Bern, 35 Murtenstrasse, 3010 Bern, Switzerland.
Favre
L
L
Wattendorf
E
E
Marti
A
A
Jaggi
R
R
Gimmi
C D
CD
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines; D002469:Cell Separation; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000235:genetics; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D019496:Cancer Vaccines; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C505658:Fasl protein, mouse; C505662:Faslg protein, rat