{"title":"Designing Cancer Immunotherapies That Engage T Cells and NK Cells.","authors":"Oleksandr Kyrysyuk, Kai W Wucherpfennig","doi":"10.1146/annurev-immunol-101921-044122","DOIUrl":null,"url":null,"abstract":"<p><p>T cells and natural killer (NK) cells have complementary roles in tumor immunity, and dual T cell and NK cell attack thus offers opportunities to deepen the impact of immunotherapy. Recent work has also shown that NK cells play an important role in recruiting dendritic cells to tumors and thus enhance induction of CD8 T cell responses, while IL-2 secreted by T cells activates NK cells. Targeting of immune evasion mechanisms from the activating NKG2D receptor and its MICA and MICB ligands on tumor cells offers opportunities for therapeutic intervention. Interestingly, T cells and NK cells share several important inhibitory and activating receptors that can be targeted to enhance T cell- and NK cell-mediated immunity. These inhibitory receptor-ligand systems include CD161-CLEC2D, TIGIT-CD155, and NKG2A/CD94-HLA-E. We also discuss emerging therapeutic strategies based on inhibitory and activating cytokines that profoundly impact the function of both lymphocyte populations within tumors.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":"41 ","pages":"17-38"},"PeriodicalIF":26.9000,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159905/pdf/nihms-1873672.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-immunol-101921-044122","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/11/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
T cells and natural killer (NK) cells have complementary roles in tumor immunity, and dual T cell and NK cell attack thus offers opportunities to deepen the impact of immunotherapy. Recent work has also shown that NK cells play an important role in recruiting dendritic cells to tumors and thus enhance induction of CD8 T cell responses, while IL-2 secreted by T cells activates NK cells. Targeting of immune evasion mechanisms from the activating NKG2D receptor and its MICA and MICB ligands on tumor cells offers opportunities for therapeutic intervention. Interestingly, T cells and NK cells share several important inhibitory and activating receptors that can be targeted to enhance T cell- and NK cell-mediated immunity. These inhibitory receptor-ligand systems include CD161-CLEC2D, TIGIT-CD155, and NKG2A/CD94-HLA-E. We also discuss emerging therapeutic strategies based on inhibitory and activating cytokines that profoundly impact the function of both lymphocyte populations within tumors.
T细胞和自然杀伤（NK）细胞在肿瘤免疫中具有互补作用，因此T细胞和NK细胞的双重攻击为加深免疫疗法的效果提供了机会。最近的研究还表明，NK 细胞在将树突状细胞募集到肿瘤中发挥着重要作用，从而增强了 CD8 T 细胞反应的诱导，而 T 细胞分泌的 IL-2 能激活 NK 细胞。针对肿瘤细胞上激活的 NKG2D 受体及其 MICA 和 MICB 配体的免疫逃避机制提供了治疗干预的机会。有趣的是，T 细胞和 NK 细胞共享几种重要的抑制性和激活性受体，可以通过靶向这些受体来增强 T 细胞和 NK 细胞介导的免疫力。这些抑制性受体配体系统包括 CD161-CLEC2D、TIGIT-CD155 和 NKG2A/CD94-HLA-E。我们还讨论了基于抑制性和激活性细胞因子的新兴治疗策略，这些细胞因子对肿瘤内两种淋巴细胞群的功能都有深远影响。
期刊介绍：
The Annual Review of Immunology, in publication since 1983, focuses on basic immune mechanisms and molecular basis of immune diseases in humans. Topics include innate and adaptive immunity; immune cell development and differentiation; immune control of pathogens (viruses, bacteria, parasites) and cancer; and human immunodeficiency and autoimmune diseases. The current volume of this journal has been converted from gated to open access through Annual Reviews' Subscribe to Open program, with all articles published under a CC BY license.
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