<b><i>Background:</i></b> Breast carcinoma is the most common malignant disease in the female population and one of the leading causes of death among women worldwide. One crucial hallmark of cancer is chronic inflammation where the immunosuppressive environment is dominant. The immunosuppressive environment is largely achieved by the interaction of tumor cells and infiltrating leukocytes. <b><i>Summary:</i></b> Usually, human macrophages and natural killer cells are involved in antitumor immunity. The therapeutic potential of this population against cancers has stimulated their study and led to the discovery of several different tumor-associated macrophages and natural killer cell subsets, each of which is endowed with different immunoregulatory functions. Both heterogeneity and plasticity of the tumor-associated macrophages and natural killer cell compartment, which are both tightly linked to the tumor microenvironment of different breast cancer types. <b><i>Key Messages:</i></b> The identification of specific tumor-associated macrophages and natural killer cell subsets endowed with particular functional capabilities might help monitor tumor-mediated responses in breast cancer patients. Currently, one of the most used strategies for breast cancer of newly diagnosed patients is neoadjuvant chemotherapy.
BackgroundThe aim of this study was to determine the frequency of exposure to different sensitizing events (SEs) and to assess their effects on human leucocyte antigen (HLA) alloimmunization in transplant candidates using two different HLA antibody screening techniques: complement-dependent cytotoxicity (CDC) and Luminex.MethodsThis retrospective study included HLA antibody screening results for 163 patients on the kidney transplant waiting list (WL) tested from March 2012 until the end of December 2015 at the Tissue Typing Laboratory, Rijeka, Croatia. All sera samples were tested using the CDC and Luminex techniques in parallel.ResultsTwo-thirds of the patients [114 (70%)] on the WL were exposed to transfusions, pregnancies and/or kidney transplant. The pre-transplant sera of 104 (63.80%) patients were negative for antibodies. In the sera of 23 (14.11%) patients, HLA antibodies were detected by CDC and Luminex and in the sera of 36 (22.09%) patients by Luminex only.ConclusionIn patients on kidney WL, previous organ transplantation represents the strongest immunogenic stimulus, followed by blood transfusions (the most frequent SE) and pregnancies. Although Luminex is more sensitive than CDC in HLA antibody detection, the decision on unacceptable HLA antigens in WL patients has to be based on the results of both assays and the patient’s immunization history.
Evaluation of the HLA antibody status in patients on a waiting list for organ transplantation should be based on the results of the both CDC and Luminex® (or other sensitive) assays in accordance to information about patient's clinical status and exposure to immunizing events.
Globally, breast cancer is the main cause of death among female cancer patients. The tumorinfiltrating lymphocytes (TILs) in breast cancer are associated with a more favorable outcome of a disease. Natural killer (NK) cells are important cytotoxic cells involved in tumor immunosurveillance, causing the direct killing of tumor cells. In solid tumors, peripheral NK cells and tumor-infiltrating NK cells display an altered characterized by reduced cytotoxicity or anergy. The goal of this study was to investigate the NK cells' phenotype and activation status in order to get into the pathological process of breast cancer subtypes. In our study, the normal tissues and tumoral breast tissue were fixed in formalin, embedded in paraffin, and the phenotypic marker CD56 and proinflammatory cytokine IL-15 were identified by immunohistology. The distribution and expression of receptors repertoire (NKG2A, NKG2C, NKp46, CD94, CD69, and CD107a) were investigated in peripheral NK cells of mononuclear cells by flow cytometry. mRNA of cytolytic mediators was determined by real-time PCR. The frequency of CD56+ and IL-15+ cells were significantly higher in triple-negative breast cancer tissue. The frequency of NK cell activating receptors was decreased in investigated breast cancer subtypes while the inhibitory NKG2A receptor was increased. Decreased percentage of CD69+/CD107a+ in NK cells could indicate lower cellular activation and cytotoxicity. In luminal B breast cancer, the mRNA of cytolytic mediators was upregulated. In conclusion, modulation of activation status in tumor-infiltration NK cells could be involved in the pathogenesis of molecular breast cancer subtypes. This highlights the importance of NK cells as an appropriate target for potent anti-tumor response in the immunosuppressive tumor microenvironment of breast cancer.
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