Breast cancer is one of the most common female malignancies in many countries . Multidisciplinary approaches, including surgery, conventional chemotherapy, radiotherapy, endocrine therapy, bisphosphonates, and HER-2/neu directed therapy, have been used widely for the patients’ treatment; however, a large number of patients responds poorly to these approaches. It is important to expand repertoire of new molecular markers for further therapeutic strategies.
Effective immune response involving T-cell activation defenses normal cells against pathogens through producing cytokines or cytotoxicity. However, immune response to tumor cells is usually inadequate or inactivated, which is one of the most common reasons caused tumor growth, invasion and metastasis [2, 3]. Co-stimulatory molecules expressed by antigen presenting cells or tumor cells play a large role in T-cell activation: stimulatory molecules activated T-cell response, and inhibitory molecules suppressed it. When lacking stimulatory molecules (CD80 and CD86) expression or over-expressing inhibitory molecules (B7-H1, B7-H3 and B7-H4) in tumor cells, T-cell is induced to be tolerant or anergic [4, 5], which is considered to be associated with immune response escape during cancer development [6–9]. Therefore, studies of co-stimulatory molecules in tumors are not only critical for understanding mechanisms involving in tumor associated immune response, but also helpful for finding new targets of tumor therapy.
Immunoglobulin-like transcripts (ILTs; also referred to as leukocyte immunoglobulin-like receptors) represent a novel immunoglobulin superfamily of both inhibitory and stimulatory receptors involved in immune surveillance [10–12], and are closely related to the killer-cell inhibitory receptor family mapping to the leukocyte receptor complex [13–15]. ILT4, expressed by monocytes, dendritic cells (DCs) and endothelial cells (ECs), has a long cytoplasmic tail containing immunoreceptor tyrosine-based inhibitory motifs which mediates inhibition of cell activation by recruiting tyrosine phosphatase SHP-1 [12, 16]. Upregulation of ILT4 on professional and non-professional antigen-presenting cells (APCs) can induce CD4+ T-helper cells anergy; decrease stimulatory molecules expression in T cells [17–19]; and elicit the differentiation of Ag-specific CD4+ and CD8 + Treg cells . In general, the biological function of ILT4 is considered to inhibit the immune response.
The expression of ILTs in cancer cells and their important role in tumor progression become more and more attractive these days. ILT4 is found to be expressed in NSCLC cells  with less number of Tumor Infiltrating Lymphocytes (TILs) infiltrated; and the expression of ILT3 or ILT4 in neoplastic B cells is associated with lymphoid tissue involvement in chronic lymphocytic leukemia . However, little is known about the expression and function of ILT4 in other human carcinomas, such as, breast cancers.
IL-10, a pleiotropic cytokine, primarily produced by Th2 cells and Treg cells, has been reported to induce ILT4 upregulation in monocytes and DCs, rendering them tolerogenic [23, 24]. Furthermore, in human endothelial cells (ECs), IL-10 also upregulates ILT3/ILT4 expression; and suppresses T-cell co-stimulatory potential of human ECs . However, there is no study to determinate the relationship between ILT4 and IL-10 expression in tumor tissues and assay their role in tumor progression. We here aimed to evaluate the immunohistochemistry expression of ILT4 and IL-10 in a series of invasive ductal and lobular breast carcinomas; analyze the association between ILT4 and IL-10 expression; and discuss their role in breast cancer development through assaying the relationship between ILT4/IL-10 expression and prognostic factors. We hope our findings may be the preliminary experiment for further study on IL-10 and ILT4 function in human breast cancer.