Association between the expression of IL-10 and T cell activation proteins loss in early breast cancer patients

Abstract

Breast cancer patients may express abnormal cellular immune responses affecting their immunological competence. The analysis of immunological parameters may be useful as indicators of T cell function. To determine the expression of lymphocyte activation proteins and cytokines in tumor and non-metastatic axillary lymph nodes, 30 breast cancer patients were monitored. CD3 polypeptides, PTKs (protein tyrosine kinases) and phosphorylated tyrosines were studied by Western Blot and cytokines mRNA expression was determined by RT-PCR (reverse transcription-polymerase chain reaction). This group of patient had shown high immunohistochemistry expression of IL-10 in tumors. Activation proteins were mainly expressed in involved lymph nodes comparing with their expression in tumors. The differences in expression of CD3 polypeptides and p56(lck) between both locations were significant. There was no statistical association between PTKs and IL-10 in the tumor but more than 50% of cases who express IL-10 lost p56(lck), p59(fyn). A direct association between IL-10 and CD3-polypeptides was observed, however 52.2% of patients who express IL-10 did not express 41 kDa CD3-zeta form. IL-10 mRNA was detected in more than 50% of tumors contrary to the prevalence of type 1 cytokines in regional nodes (40%). The lack of expression of lymphocyte activations proteins and the high expression of IL-10 suggest a downregulation on T cells function in the tumors. These results are useful in order to understand the local immune response that would be key in the control of the tumor progression.

Clinical implication of human leukocyte antigen (HLA)‐F expression in breast cancer

“…Residual cancer cells can be eliminated by effector cells after recognition by the host immune system in breast cancer as well as in other cancers . The underlying mechanism mediated by the suppression of the anti‐tumor immune system has been elucidated, and suppression of the host immune system is known to induce tumor relapse postoperatively . The postoperative relapse involving an immunological mechanism is difficult to eliminate because of the stimulation of residual cancer cells.…”

“…5,6 The underlying mechanism mediated by the suppression of the anti-tumor immune system has been elucidated, and suppression of the host immune system is known to induce tumor relapse postoperatively. [7][8][9][10] The postoperative relapse involving an immunological mechanism is difficult to eliminate because of the stimulation of residual cancer cells. Among the mechanisms by which tumors evade the anticancer host immune system, ectopic expression of non-classical human leukocyte antigen (HLA) class Ib proteins (HLA-E, HLA-F and HLA-G) on cancer cells has been studied extensively.…”

Role of interleukin-10 in the regulation of tumorigenicity of a T cell lymphoma

“…For example, in breast cancer, the expression of IL-10 was proven to be elevated through immunohistochemistry [43]. In addition, it was shown that patients with leukemias including acute myeloid leukemia (AML) and adult T-cell leukemia/lymphoma (ATLL) exhibited high levels of IL-10 in their serum [44,45].…”

Down-regulation of CD3zeta is a breast cancer biomarker associated with immune suppression

“…Breast cancer pathogenesis involves multiple factors including genetic, environmental, dietetic and immunologic (Hill et al, 2004;Grant et al, 2007;Llanes-Fernandez et al, 2009). Deficient DNA repair contributes to accumulation of DNA damage resulting in breast carcinogenesis and LOH (loss of heterozygosity), combined with allele silencing of tumour suppressor genes, may play a role in the progression of breast cancer (Driouch et al, 1997;Ahomadegbe et al, 2000).…”