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Role of Fas ligand expression in promoting escape from immune rejection in a spontaneous tumor model
Author(s) -
Céfai Daniel,
Favre Luc,
Wattendorf Elise,
Marti Andreas,
Jaggi Rolf,
Gimmi Claude D.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1074>3.0.co;2-o
Subject(s) - immune system , downregulation and upregulation , fas ligand , in vivo , tumor progression , immunotherapy , cancer research , biology , apoptosis , immunology , immune escape , major histocompatibility complex , mhc class i , cancer , programmed cell death , gene , biochemistry , genetics , microbiology and biotechnology
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. © 2001 Wiley‐Liss, Inc.