Pro-tumoral immune cell alterations in wild type and -deficient mice in response to 4T1 breast carcinomas.

To assess mechanisms responsible for breast carcinoma metastasis, 4T1 breast carcinomas were grown orthotopically in wild type or knockout mice. Tumor growth, metastasis, vascular characteristics and immune cell properties were analyzed. Absence of did not affect tumor growth although it increased lung metastasis. knockout mouse tumors showed decreased redness and less developed vascular plexa located at the periphery of the tumors. No difference in overall tumor vascular density, leakage or pericyte coverage was noted between the genotypes although the average vessel size was smaller in the knockout. Tumors induced an increase of CD11b cells in spleen, lymph node, thymus, bone marrow and blood. Numbers of knockout CD11b/CD8 cells were decreased in lymph nodes and bone marrow of tumor bearing mice. Mice with tumors had reduced numbers of CD4 lymphocytes in blood/lymphoid organs, whereas in most of these locations the proportion of CD4 cells co-expressing FoxP3 was increased, suggesting a relative increase in Treg cells. This finding was reinforced by increased blood interleukin-35 (IL-35) in wild type tumor bearing mice. knockout blood showed in addition an increased proportion of IL-35 expressing Treg cells, supporting the notion that absence of further promotes tumor evasion from immune cell recognition. This could explain the increased number of lung metastases observed under these conditions. In conclusion, 4T1 tumors alter immune cell responses that promote tumor expansion, metastasis and escape from T cell recognition in an dependent manner.