Mechanisms of tumor-induced immunosuppression: evidence for contact-dependent T cell suppression by monocytes.
BACKGROUND
The progressive growth of tumors in mice is accompanied by down-regulation of specific T cell responses. The factors involved in this suppression are not completely understood. Here, we have developed a model to examine the role of host immune effector cells in the inhibition of T cell function. In this model, progressive growth of a colon carcinoma line, CT26, is accompanied by loss of T cell response to alloantigens in both cytolytic and proliferation assays.


METHODS
The CT26 tumor was inoculated into BALB/c syngeneic mice. Tumor growth, cytolytic T cell responses, lymphocyte proliferation, and flow cytometric analysis was performed in tumor-bearing animals 7 or 28 days after tumor inoculation.


RESULTS
Spleen cells from tumor-bearing mice were found to suppress the proliferative response of spleen cells from normal mice to alloantigens. Examination of the spleen cell population by FACS analysis revealed an increase in the percentage of monocytes as defined by expression of CD11b, the Mac-1 antigen. Removal of the Mac-1-positive cells from the tumor-bearing hosts spleen relieved suppression of the tumor-bearing mouse spleen cell proliferative response to alloantigens, and addition of the Mac-1-positive enriched cells suppressed proliferation of normal T cells in response to alloantigens. Cell contact was required for this inhibition.


CONCLUSIONS
Tumor induction of suppressive monocytes plays an important role in the general immunosuppression noted in animals bearing CT26 tumors. Identification of the mechanisms responsible for this effect and reversal of tumor-induced macrophage suppression may facilitate efforts to develop effective immunotherapy for malignancy.
Jaffe
M L
ML
Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109, USA.
Arai
H
H
Nabel
G J
GJ
D000818:Animals; D018845:CD11 Antigens / Q000276:immunology; D002455:Cell Division; D003260:Contact Inhibition / Q000276:immunology / Q000502:physiology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism*; D009374:Neoplasms, Experimental; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D018845:CD11 Antigens; D015395:Histocompatibility Antigens Class I