Combination Immunotherapy: Taking Cancer Vaccines to the Next Level.
Combination Immunotherapy: Taking Cancer Vaccines to the Next Level.
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DOI：
10.3389/fimmu.2018.00610
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发表时间：
2018
影响因子：
7.3
通讯作者：
Khanna KM
中科院分区：
文献类型：
--
作者：
Grenier JM;Yeung ST;Khanna KM
随着检查点阻断疗法的出现，免疫疗法现在是治疗某些癌症的关键方式。虽然一些患者对检查点封锁反应良好，但许多患者没有，因此需要其他形式的治疗。针对恶性肿瘤的疫苗接种一直是科学界长期追求的目标。对于具有微生物病因的癌症，疫苗接种在降低疾病发生率方面非常有效。然而，针对已确定的恶性肿瘤的疫苗接种在很大程度上令人失望。在这篇综述中，我们讨论了开发治疗癌症（特别是黑色素瘤）的多种疫苗模式的努力。最近的研究表明，针对患者特异性肿瘤突变的疫苗可能比针对未突变蛋白质的疫苗更相关。尽管如此，肿瘤细胞利用许多策略来逃避宿主免疫。只有当疫苗与靶向肿瘤免疫逃避机制的其他疗法结合时，癌症疫苗接种的全部潜力才有可能实现。通过调节抑制性分子、调节性免疫细胞以及T细胞的代谢资源和需求，科学家和临床医生可以确保疫苗刺激的T细胞在免疫抑制性肿瘤微环境中发挥完全功能。
With the advent of checkpoint blockade therapies, immunotherapy is now a critical modality for the treatment of some cancers. While some patients respond well to checkpoint blockade, many do not, necessitating the need for other forms of therapy. Vaccination against malignancy has been a long sought goal of science. For cancers holding a microbial etiology, vaccination has been highly effective in reducing the incidence of disease. However, vaccination against established malignancy has been largely disappointing. In this review, we discuss efforts to develop diverse vaccine modalities in the treatment of cancer with a particular focus on melanoma. Recent work has suggested that vaccines targeting patient-specific tumor mutations may be more relevant than those targeting unmutated proteins. Nonetheless, tumor cells utilize many strategies to evade host immunity. It is likely that the full potential of cancer vaccination will only be realized when vaccines are combined with other therapies targeting tumor immunoevasive mechanisms. By modulating inhibitory molecules, regulatory immune cells, and the metabolic resources and demands of T cells, scientists and clinicians can ensure vaccine-stimulated T cells are fully functional within the immunosuppressive tumor microevironment.