Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice.
Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8+ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-alpha and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3 gamma and completely lacked CD3 zeta, which was replaced by the Fc epsilon gamma-chain. Expression of the tyrosine kinases p56lck and p59fyn was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.
Mizoguchi
H
H
Biological Response Modifiers Program, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702.
O'Shea
J J
JJ
Longo
D L
DL
Loeffler
C M
CM
McVicar
D W
DW
Ochoa
A C
AC
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D016827:CD8 Antigens / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D003110:Colonic Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D053804:Granzymes; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000302:isolation & purification / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D017252:CD3 Complex; D016827:CD8 Antigens; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; D002118:Calcium