Mice bearing late-stage tumors have normal functional systemic T cell responses in vitro and in vivo.
Immune suppression in tumor-bearing hosts is considered to be one factor causally associated with the growth of antigenic tumors. Support for this hypothesis has come from reports that spleen T cells in tumor-bearing mice are deficient in either priming or effector phase functions. We have reexamined this hypothesis in detail using multiple murine tumor models, including transplantable adenocarcinoma, melanoma, sarcoma, and thymoma, and also a transgenic model of spontaneous breast carcinoma. In both in vitro and in vivo assays of T cell function (proliferation, cytokine production, induction of CD8+ alloreactive CTL, and development of anti-keyhole limpet hemocyanin CD4+ T cells, rejection of allogeneic or syngeneic regressor tumors, respectively) we show that mice bearing sizable tumor burdens are not systemically suppressed and do not have diminished T cell functions. Therefore, if immune suppression is a causal function in the growth of antigenic tumor, the basis for escape from immune destruction is likely to be dependent upon tumor-induced T cell dysfunction at the site of tumor growth.
Radoja
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S
Department of Cell Biology and Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Rao
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TD
Hillman
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D
Frey
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AB
D000818:Animals; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013163:Splenomegaly / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018800:Thy-1 Antigens / Q000096:biosynthesis
D016207:Cytokines; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin