Haynes Nicole M, van der Most Robbert G, Lake Richard A, Smyth Mark J
Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia.
Curr Opin Immunol. 2008 Oct;20(5):545-57. doi: 10.1016/j.coi.2008.05.008. Epub 2008 Jun 23.
Tumors can acquire mutations or hijack regulatory pathways of the host immune system to render them resistant to immune attack. Standard first line therapies such as chemotherapy and radiation were not thought to provoke natural immunity to cancer, but recent findings demonstrating that dying tumor cells present and release key signals to stimulate or evade neighboring leukocytes are challenging that view. Killing tumor cells in a manner that provides danger signals and tumor antigens in the right context promotes the engagement of innate and adaptive immunity; however, this response alone will not be effective against established cancer. Coincidently driving the immune response with specific monoclonal antibodies and other immunomodulators that activate and mature dendritic cells and co-stimulate T cells and other lymphocytes is one approach. Additionally releasing immune checkpoints and inhibiting tumor-derived molecules that prevent effective tumor immunity is another. Combined these approaches have enormous potential to improve the current outcomes from conventional cancer therapy.
肿瘤可获得突变或劫持宿主免疫系统的调节途径,使其对免疫攻击产生抗性。化疗和放疗等标准一线疗法过去被认为不会激发对癌症的天然免疫,但最近的研究结果表明,垂死的肿瘤细胞会呈现并释放关键信号以刺激或逃避邻近的白细胞,这一观点正受到挑战。以在正确背景下提供危险信号和肿瘤抗原的方式杀死肿瘤细胞,可促进固有免疫和适应性免疫的参与;然而,仅靠这种反应对已形成的癌症并不有效。用特异性单克隆抗体和其他免疫调节剂来驱动免疫反应,这些调节剂可激活并使树突状细胞成熟,共同刺激T细胞和其他淋巴细胞,这是一种方法。此外,释放免疫检查点并抑制阻止有效肿瘤免疫的肿瘤衍生分子是另一种方法。将这些方法结合起来,有巨大潜力改善传统癌症治疗的当前效果。