Immune dysfunction and micrometastases in women with breast cancer

Abstract

Cytokines produced by T lymphocytes are critical to the efficacy of a given immune response and dysregulation of immune responses may play a role in cancer progression. We assessed the intracellular cytokine profiles of T cells in the peripheral blood of women with breast cancer and explored the relationship of these responses with the presence of cancer in lymph nodes and bone marrow. Peripheral blood lymphocytes from 84 patients and 26 healthy volunteers were analyzed by 4-color flow cytometry for surface markers and for intracellular cytokines. Bone marrow samples from some of these patients were also collected and analyzed for the presence of epithelial cells (micrometastases) by flow cytometry. The percentages of both CD4(+) and CD8(+) cells producing type1 (IL-2, IFN-gamma or TNF-alpha) and type 2 (IL-4) were significantly lower in patients with breast cancer compared to healthy controls. These results indicate a general immune dysfunction in these patients as opposed to a shift in the balance of type1 and type2 cells. These dysregulated T cell responses did not correlate with age, stage of disease, or nodal status. However, we did observe a correlation between number of micrometastases in the bone marrow and T cell responsiveness.

T‐Helper (Th) 1/ Th2 Imbalance in the Peripheral Blood of Dogs with Malignant Tumor

“…The difference in the percentage of Th2 in CD4ϩ cells and the mean ratio of Th1/Th2 between patients with metastatic tumor and patients without metastatic tumor was not significant. A similar result was reported in human breast cancer (3). It may be a trend that patient with metastatic tumor showed more suppressed Th1 immune responses.…”

Management of the intact breast primary in the setting of metastatic disease

“…Malignancy-induced immune system defects have been demonstrated in cytokine production, recognition of foreign antigens, and T and B cell function. A correlation between the number of micrometastases (defined as circulating epithelial cells in the bone marrow) and the degree of immunosuppression has been demonstrated [39]. Furthermore, using a mouse model, Danna et al were able to demonstrate that removal of an intact primary mammary tumor in the setting of metastatic disease could restore the immunocompetence of the host [40].…”

Evaluation of the scientific results of the study entitled “Opportunities for surgical treatment of patients with stage IV breast cancer” performed by Russian Society of Oncomammologists (RSOM)

“…Уста-новлено, что некоторые опухоли, в том числе РМЖ, способны индуцировать иммуносупрессию и за счет секреции цитокинов ускорять прогрессирование бо-лезни. Выявлена прямая корреляция степени имму-носупрессии и количества циркулирующих микроме-тастазов опухоли [28].…”