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胃癌的免疫疗法

Immunotherapy in gastric cancer.

作者信息

Matsueda Satoko, Graham David Y

机构信息

Satoko Matsueda, Cancer Vaccine Development Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Fukuoka 830-0011, Japan.

出版信息

World J Gastroenterol. 2014 Feb 21;20(7):1657-66. doi: 10.3748/wjg.v20.i7.1657.

Abstract

Gastric cancer is the second most common of cancer-related deaths worldwide. In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved, survival rates remain poor. Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer, prostate cancer and melanoma. Here, we provide an overview of concepts of modern cancer immunotherapy including the theory, current approaches, remaining hurdles to be overcome, and the future prospect of cancer immunotherapy in the treatment of gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies, monoclonal antibody therapies have all been used with some initial successes in gastric cancer. However, to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response. Here, we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy. We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment. We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells. Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being. Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.

摘要

胃癌是全球癌症相关死亡的第二大常见原因。在大多数情况下,胃癌在诊断时已处于晚期,尽管药物和手术治疗有所改善,但生存率仍然很低。癌症免疫疗法已成为一种强大且有前景的癌症治疗临床方法,并在乳腺癌、前列腺癌和黑色素瘤治疗中取得了重大成功。在此,我们概述现代癌症免疫疗法的概念,包括理论、当前方法、有待克服的障碍以及癌症免疫疗法在胃癌治疗中的未来前景。适应性细胞疗法、癌症疫苗、基因疗法、单克隆抗体疗法在胃癌治疗中都有一定的初步成功应用。然而,迄今为止,胃癌治疗的结果令人失望,因为当前方法往往不能有效地刺激免疫反应,尽管存在可测量的免疫反应,但肿瘤仍继续生长。在此,我们讨论免疫疗法靶点的识别以及生物标志物在前瞻性识别合适受试者或免疫疗法中的作用。我们还讨论肿瘤细胞逃避宿主免疫监视并产生免疫抑制性肿瘤微环境的分子机制。我们展示了相关进展如何提供克服免疫抑制机制的工具,包括使用单克隆抗体阻断通常在T细胞表面表达的负调节因子,这些负调节因子会限制细胞毒性T细胞的激活和增殖。免疫疗法已取得巨大进步,并正成为人类医疗保健和福利等领域的一个重要因素。进展迅速,确保了胃癌免疫疗法的未来前景光明。

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