Biological and Health Sciences Center, Federal University of Maranhão, Avenida dos Portugueses, 1966, Bacanga, São Luis, Brazil.
Pérola Byington Hospital, Avenida Brigadeiro Luis Antonio, 683 São Paulo, Brazil.
Mediators Inflamm. 2019 Nov 18;2019:8346930. doi: 10.1155/2019/8346930. eCollection 2019.
Dendritic cells (DCs) are the most efficient - and link the innate immune sensing of the environment to the initiation of adaptive immune responses, which may be directed to either acceptance or elimination of the recognized antigen. In cancer patients, though DCs would be expected to present tumor antigens to T lymphocytes and induce tumor-eliminating responses, this is frequently not the case. The complex tumor microenvironment subverts the immune response, blocks some effector mechanisms, and drives others to support tumor growth. Chronic inflammation in a tumor microenvironment is believed to contribute to the induction of such regulatory/tolerogenic response. Among the various mediators of the modulatory switch in chronic inflammation is the "antidanger signal" chaperone, heat shock protein 27 (Hsp27), that has been described, interestingly, to be associated with cell migration and drug resistance of breast cancer cells. Thus, here, we investigated the expression of Hsp27 during the differentiation of monocyte-derived DCs (Mo-DCs) from healthy donors and breast cancer patients and evaluated their surface phenotype, cytokine secretion pattern, and lymphostimulatory activity. Surface phenotype and lymphocyte proliferation were evaluated by flow cytometry, interferon- (IFN-) , and interleukin- (IL-) 10 secretion, by ELISA and Hsp27 expression, by quantitative polymerase chain reaction (qPCR). Mo-DCs from cancer patients presented decreased expression of DC maturation markers, decreased ability to induce allogeneic lymphocyte proliferation, and increased IL-10 secretion. In coculture with breast cancer cell lines, healthy donors' Mo-DCs showed phenotype changes similar to those found in patients' cells. Interestingly, patients' monocytes expressed less GM-CSF and IL-4 receptors than healthy donors' monocytes and Hsp27 expression was significantly in patients' Mo-DCs (and in tumor samples). Both phenomena could contribute to the phenotypic bias of breast cancer patients' Mo-DCs and might prove potential targets for the development of new immunotherapeutic approaches for breast cancer.
树突状细胞（DCs）是最有效的，它们将环境的先天免疫感应与适应性免疫反应的启动联系起来，适应性免疫反应可能指向对识别抗原的接受或消除。在癌症患者中，尽管 DC 应该将肿瘤抗原呈递给 T 淋巴细胞并诱导肿瘤消除反应，但事实并非如此。复杂的肿瘤微环境颠覆了免疫反应，阻断了一些效应机制，并促使其他机制支持肿瘤生长。肿瘤微环境中的慢性炎症被认为有助于诱导这种调节/耐受反应。在慢性炎症的调节开关的各种介质中，有一种“抗危险信号”伴侣热休克蛋白 27（Hsp27），有趣的是，它与乳腺癌细胞的迁移和耐药性有关。因此，在这里，我们研究了健康供体和乳腺癌患者来源的单核细胞衍生树突状细胞（Mo-DC）分化过程中 Hsp27 的表达，并评估了它们的表面表型、细胞因子分泌模式和淋巴刺激活性。通过流式细胞术评估表面表型和淋巴细胞增殖，通过 ELISA 和定量聚合酶链反应（qPCR）评估干扰素-（IFN-）和白细胞介素-（IL-）10 分泌，通过定量聚合酶链反应（qPCR）评估 Hsp27 表达。与健康供体相比，癌症患者的 Mo-DC 表现出 DC 成熟标志物表达降低、诱导同种异体淋巴细胞增殖能力降低和 IL-10 分泌增加。在与乳腺癌细胞系共培养时，健康供体的 Mo-DC 表现出与患者细胞相似的表型变化。有趣的是，与健康供体的单核细胞相比，患者的单核细胞表达的 GM-CSF 和 IL-4 受体较少，并且患者的 Mo-DC 中 Hsp27 的表达显著增加（和肿瘤样本中）。这两种现象都可能导致乳腺癌患者 Mo-DC 的表型偏向，并可能成为开发乳腺癌新免疫治疗方法的潜在靶点。
