Subramaniam Deepa S, Liu Stephen V, Giaccone Giuseppe
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA.
Discov Med. 2016 Apr;21(116):267-74.
Our understanding of tumor immunology has exploded in the past 3 decades. The complex relationships between tumor cells, the tumor microenvironment and the immune system cells, especially the cytotoxic and helper T cells and the regulatory T cells are beginning to be elucidated. In this review, we will attempt to provide a brief primer of tumor immunology. Cytokine therapy has historically been the mainstay of immunotherapy in cancers such as melanoma and kidney cancer. We will review some of the advances made with cancer vaccines, with a focus on peptide vaccines, tumor cell vaccines and immune cell vaccines. The pros and cons of nucleic acid-based vaccines including DNA and RNA vaccines will be discussed. Adoptive cell therapy has made significant progress utilizing chimeric antigen-receptor transduced T cells, especially in hematologic malignancies. We will also consider the key targets in checkpoint inhibition, and summarize some of the preclinical and clinical data with respect to checkpoint inhibition. Progress made in the novel immunotherapeutic approach of oncolytic viral therapy will be analyzed. PDL-1 expression by tumor cells and tumor infiltrating lymphocytes has been looked at as a biomarker in clinical trials. Limitations to such an approach and potential candidates for future predictive biomarkers of response to immunotherapy and biomarkers of autoimmunity and adverse reactions will be considered.
在过去30年里,我们对肿瘤免疫学的理解有了飞跃式的发展。肿瘤细胞、肿瘤微环境与免疫系统细胞之间的复杂关系,尤其是细胞毒性T细胞、辅助性T细胞和调节性T细胞之间的关系,正开始得到阐明。在这篇综述中,我们将尝试提供一份肿瘤免疫学的简要入门介绍。细胞因子疗法一直以来都是黑色素瘤和肾癌等癌症免疫治疗的主要手段。我们将回顾癌症疫苗取得的一些进展,重点关注肽疫苗、肿瘤细胞疫苗和免疫细胞疫苗。还将讨论包括DNA和RNA疫苗在内的核酸疫苗的优缺点。过继性细胞疗法利用嵌合抗原受体转导的T细胞取得了显著进展,尤其是在血液系统恶性肿瘤方面。我们还将探讨检查点抑制的关键靶点,并总结一些关于检查点抑制的临床前和临床数据。将分析溶瘤病毒疗法这种新型免疫治疗方法取得的进展。肿瘤细胞和肿瘤浸润淋巴细胞的PDL-1表达在临床试验中被视为一种生物标志物。将考虑这种方法的局限性以及未来免疫治疗反应预测生物标志物、自身免疫和不良反应生物标志物的潜在候选物。