Targets of Immune Escape Mechanisms in Cancer: Basis for Development and Evolution of Cancer Immune Checkpoint Inhibitors

被引:56
|
作者
Dutta, Shovan [1 ]
Ganguly, Anirban [2 ]
Chatterjee, Kaushiki [3 ]
Spada, Sheila [4 ]
Mukherjee, Sumit [5 ]
机构
[1] Cleveland Clin, Lerner Res Inst, Ctr Immunotherapy & Precis Immuno Oncol CITI, Cleveland, OH 44195 USA
[2] All India Inst Med Sci, Dept Biochem, Deoghar 814152, India
[3] Weill Cornell Med, Dept Med, New York, NY 10021 USA
[4] Weill Cornell Med, Dept Radiat Oncol, New York, NY 10065 USA
[5] Albert Einstein Coll Med, Dept Cardiothorac & Vasc Surg, Bronx, NY 10461 USA
来源
BIOLOGY-BASEL | 2023年 / 12卷 / 02期
关键词
cancer treatment; immune response; cancer therapeutic strategy; tumor immune escape; immune-oncology; tumor immune microenvironment; immune checkpoint inhibitors; mRNA cancer immunotherapy; CRISPR-Cas9 cancer immunotherapy; REGULATORY T-CELLS; HLA CLASS-I; ADENOSINE RECEPTOR ANTAGONIST; MONO-ADP-RIBOSYLTRANSFERASE; PROMOTES TUMOR PROGRESSION; ACTIVATION GENE-3 LAG-3; GRADE OVARIAN-CARCINOMA; FACTOR-KAPPA-B; HODGKIN-LYMPHOMA; DENDRITIC CELLS;
D O I
10.3390/biology12020218
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Simple Summary The tumor immune escape mechanisms are key factors in cancer progression and metastasis. They are an undeniable hurdle for successful cancer treatment in patients. It has been widely recognized that cancer cells can escape immune surveillance and antitumor immunity. Despite host immunity, tumor cells can escape antitumor immune cell responses by several different mechanisms, such as the loss of the antigen presentation capacity by some immune cells, which promotes tumor progression and resistance to immunotherapy. A few monotherapies or combinational therapies have been approved for use in cancer treatment, but the majority of patients are not responsive to currently used immunotherapies, thus presenting a need to discover new targets to achieve efficacious immune responses to benefit cancer patients. This review focuses on some of the most important classical immune checkpoint targets and also sheds light on some of the recently discovered, promising immunotherapeutic targets and strategies. Immune checkpoint blockade (ICB) has emerged as a novel therapeutic tool for cancer therapy in the last decade. Unfortunately, a small number of patients benefit from approved immune checkpoint inhibitors (ICIs). Therefore, multiple studies are being conducted to find new ICIs and combination strategies to improve the current ICIs. In this review, we discuss some approved immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and also highlight newer emerging ICIs. For instance, HLA-E, overexpressed by tumor cells, represents an immune-suppressive feature by binding CD94/NKG2A, on NK and T cells. NKG2A blockade recruits CD8+ T cells and activates NK cells to decrease the tumor burden. NKG2D acts as an NK cell activating receptor that can also be a potential ICI. The adenosine A2A and A2B receptors, CD47-SIRP alpha, TIM-3, LAG-3, TIGIT, and VISTA are targets that also contribute to cancer immunoresistance and have been considered for clinical trials. Their antitumor immunosuppressive functions can be used to develop blocking antibodies. PARPs, mARTs, and B7-H3 are also other potential targets for immunosuppression. Additionally, miRNA, mRNA, and CRISPR-Cas9-mediated immunotherapeutic approaches are being investigated with great interest. Pre-clinical and clinical studies project these targets as potential immunotherapeutic candidates in different cancer types for their robust antitumor modulation.
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页数:43
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