Ben-Baruch Adit
The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Methods Mol Biol. 2025;2926:15-34. doi: 10.1007/978-1-0716-4542-0_2.
For over the last hundred years, the scientific community has demonstrated much interest in the roles of the immune system in regulating tumor progression. Extensive research that was performed in this context has revealed that mechanisms of acquired immunity can be highly potent in eradicating cancer cells, if given the right conditions to do so. Basic and clinical studies have paved the way toward the design of sophisticated modalities that improve the ability of T cells to efficiently recognize cancer antigens (when expressed by the tumor cells) and to expand thereafter; alongside developing procedures that prevent immune suppression caused by inhibitory immune checkpoints, these approaches offer cancer patients improved immunotherapies, which increase remission and prolong survival. The current chapter provides a summary of key aspects relevant to such immunotherapies, including the following: (1) cancer vaccines that enhance cancer antigen presentation; (2) adoptive cell transfer (ACT)-based therapies, like tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor expressing T cells (CAR-T cells); and (3) immune checkpoint blockades (ICBs) that downregulate the extent of immune suppression mediated by inhibitory immune checkpoint molecules, like cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and its ligands, primarily PD-L1 (and also PD-L2). These treatments have revolutionized the immunotherapy field, demonstrating the strong power of acquired immunity in preventing tumor growth and progression, giving much hope to cancer patients worldwide.
在过去的一百多年里,科学界对免疫系统在调节肿瘤进展中的作用表现出了浓厚的兴趣。在此背景下进行的大量研究表明,如果具备合适的条件,获得性免疫机制在根除癌细胞方面可能具有很高的效力。基础研究和临床研究为设计复杂的治疗方法铺平了道路,这些方法能够提高T细胞有效识别癌症抗原(当肿瘤细胞表达时)并随后扩增的能力;同时,开发出防止由抑制性免疫检查点引起的免疫抑制的程序,这些方法为癌症患者提供了更好的免疫疗法,提高了缓解率并延长了生存期。本章总结了与此类免疫疗法相关的关键方面,包括以下内容:(1)增强癌症抗原呈递的癌症疫苗;(2)基于过继性细胞转移(ACT)的疗法,如肿瘤浸润淋巴细胞(TILs)和表达嵌合抗原受体的T细胞(CAR-T细胞);(3)免疫检查点阻断(ICB),其可下调由抑制性免疫检查点分子介导的免疫抑制程度,如细胞毒性T淋巴细胞相关蛋白4(CTLA-4)、程序性细胞死亡蛋白1(PD-1)及其配体,主要是PD-L1(还有PD-L2)。这些治疗方法彻底改变了免疫治疗领域,证明了获得性免疫在预防肿瘤生长和进展方面的强大力量,给全球癌症患者带来了很大希望。
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