Natural killer cells as a promising therapeutic target for cancer immunotherapy

Kim, Nayoung; Lee, Hyeon Ho; Lee, Hyo‐Jung; Choi, Woo Seon; Lee, Jinju

doi:10.1007/s12272-019-01143-y

Cited by 32 publications

(24 citation statements)

References 169 publications

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“…Studies have shown that the interaction of TIGIT with the poliovirus receptor (PVR) and poliovirus receptor-like 2 (PVRL2), also named CD112, Nectin-2, and PRR2, directly inhibits NK cell cytotoxicity. 92 , 101 , 102 In addition, TIGIT has immunosuppressive effects, in that it competes with DNAM-1 for nectin-like ligands. An excellent example of the nectin-like ligand is CD155, the primary ligand for TIGIT.…”

Section: Checkpoint Receptors and Ligands In Nk Cell Dysfunctionmentioning

confidence: 99%

“…CD112R is constitutively expressed on mouse NK cells, natural killer T cells, and CD8 + T cells, and also expressed on human T cells and NK cells. 101 , 158 – 160 Based on research findings, the expression of CD112R on CD16 + NK cells from human PBMCs was nearly equal to that on CD16 − NK cells. 160 CD112R was also highly expressed on NK cells from ovarian, endometrial, kidney, prostate, lung, and breast cancers.…”

Section: Checkpoint Receptors and Ligands In Nk Cell Dysfunctionmentioning

confidence: 99%

“…NK cells belong to the innate immune system and are active in the early fight against cancer through their ability to kill abnormal cells. 101 , 217 They do not require previous stimulation and can induce an effective antitumor response that is mainly mediated by specialized cell-surface receptors, indicating malignancy. 218 There is evidence from preclinical experiments and clinical trials for the development of NK cell-targeted immunotherapies (Tables 1 and 2 ) as a solution to chemo-resistant cancers, such as non-Hodgkin lymphoma.…”

Section: Nk Cell As a Promising Therapeutic Target For Cancermentioning

confidence: 99%

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Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Cao

Wang

Jin

et al. 2020

Sig Transduct Target Ther

100

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Recent studies have demonstrated the potential of natural killer (NK) cells in immunotherapy to treat multiple types of cancer. NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex. The discovery of the NK’s potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers. NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy. The effector role of these cells is reliant on the balance of inhibitory and activating signals. Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation. Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment; this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers. Accordingly, this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function, as well as their potential application in tumor immunotherapy.

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Section: Checkpoint Receptors and Ligands In Nk Cell Dysfunctionmentioning

confidence: 99%

Section: Checkpoint Receptors and Ligands In Nk Cell Dysfunctionmentioning

confidence: 99%

Section: Nk Cell As a Promising Therapeutic Target For Cancermentioning

confidence: 99%

See 1 more Smart Citation

Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Cao

Wang

Jin

et al. 2020

Sig Transduct Target Ther

100

View full text Add to dashboard Cite

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“…Cancer therapies targeting activating NKG2D, a major activating receptor for NK cells, has been shown to improve NK cell responses leading to the suppression of tumor growth and the reduced formation of metastases in various tumor types, such as melanoma, osteosarcoma and hepatocellular carcinoma (49). CAR-NK cells could be an alternative approach to receive more potent antitumor activity and less side effects (50). A study used CAR-NK cells to treat three patients with metastatic colorectal cancer.…”

Section: Natural Killer(nk) Cellsmentioning

confidence: 99%

Targeting Immune-Mediated Dormancy: A Promising Treatment of Cancer

Wang

Huang

et al. 2019

Front. Oncol.

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Immune-mediated dormancy is when the immune system keeps proliferating tumor cells unchanged, mostly via cytotoxic activity of immune cells. Cancer dormancy, especially immune-mediated dormancy, may be the explanation for tumor refractory and may be responsible for resistance to conventional chemo- and radiotherapies. Here, we will describe different scenarios as to how the immune cells and cytokines involved in cancer progression are connected with the initiation of dormancy and cancer treatment. Two distinct treatment methods, such as maintaining metastatic tumor cells dormant and awakening them, are also discussed. A better understanding of immune-mediated dormancy will help to design novel and effective immunotherapies and will likely increase the efficiency of tumor treatment inhibiting metastasis.

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“…Selective PD-1 expression on CD56 dim CD57 pos mature NK cells in some but not all healthy individuals has been reported (148) and associated with functional defects (149). However, overall expression and functional relevance of those markers on NK cells in health and disease is still unclear, and recent studies suggest that blockade of CTLA-4 and PD-1 might enhance NK cell anti-tumor activity mostly via indirect mechanisms (150). Interestingly, PD-1 also mediates T-cell exhaustion in chronic HIV infection, and dual immune checkpoint blockade targeting PD-1 and IL-10 significantly enhances NK cell function through reversal of adaptive immune exhaustion in PLWH (151).…”

Section: Recent Advances In Development Of Nk Cell-based Strategies Fmentioning

confidence: 99%

A Natural Impact: NK Cells at the Intersection of Cancer and HIV Disease

2019

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Despite efficient suppression of plasma viremia in people living with HIV (PLWH) on cART, evidence of HIV-induced immunosuppression remains, and normally benign and opportunistic pathogens become major sources of co-morbidities, including virus-induced cancers. In fact, cancer remains a primary cause of death even in virally suppressed PLWH. Natural killer (NK) cells provide rapid early responses to HIV infection, contribute substantially to disease modulation and vaccine protection, and are also major therapeutic targets for cancer immunotherapy. However, much like other lymphocyte populations, recent burgeoning evidence suggests that in chronic conditions like HIV, NK cells can become functionally exhausted with impaired cytotoxic function, altered cytokine production and impaired antibody-dependent cell-mediated cytotoxicity. Recent work suggests functional anergy is likely due to low-level ongoing virus replication, increased inflammatory cytokines, or increased presence of MHC low target cells. Indeed, HIV-induced loss of NK cell-mediated control of lytic EBV infection has been specifically shown to cause lymphoma and also increases replication of CMV. In this review, we will discuss current understanding of NK cell modulation of HIV disease, reciprocal exhaustion of NK cells, and how this may impact increased cancer incidences and prospects for NK cell-targeted immunotherapies. Finally, we will review the most recent evidence supporting adaptive functions of NK cells and highlight the potential of adaptive NK cells for cancer immunotherapy.

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Natural killer cells as a promising therapeutic target for cancer immunotherapy

Cited by 32 publications

References 169 publications

Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Targeting Immune-Mediated Dormancy: A Promising Treatment of Cancer

A Natural Impact: NK Cells at the Intersection of Cancer and HIV Disease

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