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肿瘤微环境中树突状细胞与乳腺癌的模式反应

Pattern response of dendritic cells in the tumor microenvironment and breast cancer.

作者信息

da Cunha Alessandra, Michelin Marcia A, Murta Eddie Fc

机构信息

Alessandra da Cunha, Marcia A Michelin, Eddie FC Murta, Research Oncology Institute (IPON), Federal University of the Triângulo Mineiro (UFTM), Uberaba, Minas Gerais 38025-440, Brazil.

出版信息

World J Clin Oncol. 2014 Aug 10;5(3):495-502. doi: 10.5306/wjco.v5.i3.495.

Abstract

Breast cancer (BC) is the most common malignant neoplasm and the cause of death by cancer among women worldwide. Its development, including malignancy grade and patient prognosis, is influenced by various mutations that occur in the tumor cell and by the immune system's status, which has a direct influence on the tumor microenvironment and, consequently, on interactions with non-tumor cells involved in the immunological response. Among the immune response cells, dendritic cells (DCs) play a key role in the induction and maintenance of anti-tumor responses owing to their unique abilities for antigen cross-presentation and promotion of the activation of specific lymphocytes that target neoplasic cells. However, the tumor microenvironment can polarize DCs, transforming them into immunosuppressive regulatory DCs, a tolerogenic phenotype which limits the activity of effector T cells and supports tumor growth and progression. Various factors and signaling pathways have been implicated in the immunosuppressive functioning of DCs in cancer, and researchers are working on resolving processes that can circumvent tumor escape and developing viable therapeutic interventions to prevent or reverse the expression of immunosuppressive DCs in the tumor microenvironment. A better understanding of the pattern of DC response in patients with BC is fundamental to the development of specific therapeutic approaches to enable DCs to function properly. Various studies examining DCs immunotherapy have demonstrated its great potential for inducing immune responses to specific antigens and thereby reversing immunosuppression and related to clinical response in patients with BC. DC-based immunotherapy research has led to immense scientific advances, both in our understanding of the anti-tumor immune response and for the treatment of these patients.

摘要

乳腺癌(BC)是全球女性中最常见的恶性肿瘤和癌症死亡原因。其发展,包括恶性程度和患者预后,受肿瘤细胞中发生的各种突变以及免疫系统状态的影响,免疫系统状态直接影响肿瘤微环境,进而影响与免疫反应中涉及的非肿瘤细胞的相互作用。在免疫反应细胞中,树突状细胞(DCs)由于其独特的抗原交叉呈递能力和促进靶向肿瘤细胞的特异性淋巴细胞活化的能力,在诱导和维持抗肿瘤反应中起关键作用。然而,肿瘤微环境可使DCs极化,将它们转化为免疫抑制性调节DCs,这是一种耐受性表型,会限制效应T细胞的活性并支持肿瘤生长和进展。多种因素和信号通路与癌症中DCs的免疫抑制功能有关,研究人员正在致力于解决能够规避肿瘤逃逸的过程,并开发可行的治疗干预措施,以预防或逆转肿瘤微环境中免疫抑制性DCs的表达。更好地了解BC患者中DC反应模式对于开发使DCs能够正常发挥功能的特异性治疗方法至关重要。各种研究DCs免疫疗法的研究表明其在诱导针对特定抗原的免疫反应、从而逆转免疫抑制以及与BC患者临床反应相关方面具有巨大潜力。基于DCs的免疫疗法研究在我们对抗肿瘤免疫反应的理解以及对这些患者的治疗方面都带来了巨大的科学进步。

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