Immune compartmentalization of T cell subsets in chemically-induced breast cancer.
In cancer, the phenotype and/or the function of T cells may differ according to their distribution through immune-associated tissues, namely immune compartments. Here, in N-methyl-N-nitrosourea (MNU)-induced mammary carcinomas of rat as a relevant model for human breast tumors, the impact of tumor burden on the T cell subsets populating the tumor microenvironment, the tumor-adjacent and -opposite mammary lymph nodes, and the spleen was assessed. In the tumors, ratio of CD8(+) cytotoxic and CD4(+) helper T cells were not significantly different than other immune compartments. On the other hand, most of these cells were further identified with CD4(+) CD25(hi) or CD4(+) Foxp3(+) , CD8(+) Foxp3(+) regulatory phenotype. The selective presence of Tregs in the mammary tumors but not in neighboring-mammary tissue was also confirmed by the expression of Treg-associated genes. The percentage of CD161(+) NKT cells was also significantly increased especially in the tumors and mammary lymph nodes. In the lymph nodes of tumor-bearing animals, in contrast to the spleen, total amount of CD8(+) cells and CD4(+) cells were increased but both of these compartments harbored high numbers of CD4(+) CD25(hi) Treg cells. TGF-β was determined as the major suppressive cytokine secreted by the immune cells of tumor-bearing animals, in addition, proliferation capacity of the T cells was diminished. Hence, the differential distribution of T cell subsets through the spleen, the mammary lymph nodes and the tumor mass in MNU-induced mammary tumor-bearing animals may contribute to a tumor-associated immunosuppression.
Fahmi
T
T
Department of Basic Oncology, Institute of Oncology, Hacettepe University, Ankara, Turkey.
Esendagli
G
G
Yilmaz
G
G
Kansu
E
E
Guc
D
D
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008321:Mammary Glands, Animal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D008770:Methylnitrosourea; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D008770:Methylnitrosourea