T cells from late tumor-bearing mice express normal levels of p56lck, p59fyn, ZAP-70, and CD3 zeta despite suppressed cytolytic activity.
Loss of T cell-associated signal transduction molecules has recently been implicated in immune suppression in tumor-bearing hosts. In the present study, we have examined this and related phenomenon extensively in a large number of tumor-bearing mice, analyzed individually. Splenic T cells from tumor-bearing mice were isolated and characterized with respect to the following: (a) levels of three tyrosine kinases, p56lck, p59fyn, and ZAP-70; (b) expression of CD3-zeta; (c) alloreactive responses; and (d) antigen-specific responses. Contrary to recent reports, T cells from tumor-bearing mice were observed to express normal levels of lck, fyn, ZAP-70, and CD3-zeta. Further, T cells showed healthy alloreactive and antigen-specific responses until approximately 3 wk after post tumor challenge, when the tumors constituted approximately 20% of the body weight. Alterations with respect to some parameters were observed only in mice that had been bearing larger tumors for a considerably longer period. As human tumors are unlikely to grow to such large sizes (e.g., > 20% of the total body weight), the significance of the alterations in T cell expression of lck, fyn, ZAP-70, or CD3-zeta in the immune status of cancer patients is unclear. Altogether, these results indicate that alterations in T cell signal transduction molecules do not account for the profound tumor-specific suppression observed during tumor growth.
Levey
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DL
Department of Biological Sciences, Fordham University, Bronx, New York 10458, USA.
Srivastava
P K
PK
D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D002455:Cell Division; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D007519:Isoantigens; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051076:Proto-Oncogene Proteins c-fyn; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase; D019061:src-Family Kinases / Q000032:analysis
D017252:CD3 Complex; D007519:Isoantigens; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D019061:src-Family Kinases