NK cell tumor therapy modulated by UV-inactivated oncolytic herpes simplex virus type 2 and checkpoint inhibitors

Wang, Yang; Jin, Jing; Li, Yuying; Zhou, Qin; Yao, Ruoyi; Wu, Zhen; Hu, Han Hwa; Fang, Zhizheng; Dong, Shuang; Cai, Qian; Hu, Sheng; Liu, Binlei

doi:10.1016/j.trsl.2021.10.006

Cited by 19 publications

(17 citation statements)

References 42 publications

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“…42,43 Promotion of tumor infiltration and activation of NK cells are both highly important for OV-mediated cancer therapy. 44 Other OVs, including reovirus 45 and herpesvirus, 46 also enhanced the tumor infiltration and activation of NK cells following administration and showed efficient antitumor effects in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Oncolytic adenovirus serotype 35 mediated tumor growth suppressionviaefficient activation and tumor infiltration of natural killer cells

Ono

Sakurai

Tokuoka

et al. 2022

Preprint

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Background: Oncolytic adenoviruses (OAds) mediate superior antitumor effects both by inducing direct oncolysis and activating antitumor immunity. Previously, we developed a novel OAd fully composed of human adenovirus serotype 35 (OAd35). OAd35 efficiently killed a variety of human tumor cells; however, OAd35-mediated activation of antitumor immunity remains to be evaluated. In this study, we examined whether OAd35-induced activation of immune cells contributes to the antitumor effects of OAd35. Methods: Tumor infiltration and activation of immune cells following intratumoral administration of OAd35 in tumor-bearing immune-competent and nude mice were analyzed. The involvement of natural killer (NK) cells in the tumor growth-suppression effects of OAd35 was evaluated in NK cell-depleted mice. The key signals for the OAd35-mediated tumor infiltration of NK cells were examined in interferon (IFN) alpha and beta receptor subunit 2 (IFNAR2) knockout and toll-like receptor 9 (TLR9) knockout mice. Results: OAd35 efficiently induced tumor infiltration of activated NK cells. NK cell depletion apparently hindered the OAd35-mediated tumor growth suppression. In IFNAR2 knockout mice, OAd35-induced tumor infiltration of activated NK cells was significantly attenuated. OAd35 did not induce tumor infiltration of NK cells in TLR9 knockout mice, although OAd35 significantly activated NK cells and showed tumor growth suppression in TLR9 knockout mice. Conclusions: OAd35 significantly promoted activation and tumor infiltration of NK cells, leading to OAd35-mediated efficient tumor growth suppression. The type-I IFN signal was crucial for the OAd35-mediated tumor infiltration and activation of NK cells. The TLR9 signal was highly related to tumor infiltration of NK cells, but not NK cell activation and antitumor effects of OAd35. OAd35 is expected to become a promising cancer immunotherapy agent via its enhancement of the antitumor activities of NK cells.

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Section: Discussionmentioning

confidence: 99%

Oncolytic adenovirus serotype 35 mediated tumor growth suppressionviaefficient activation and tumor infiltration of natural killer cells

Ono

Sakurai

Tokuoka

et al. 2022

Preprint

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“…Furthermore, UV-oHSV2 stimulation promoted the expression of two checkpoint molecules, one located on NK cells, NKG2A, and the other on tumor cells, HLA-E. This finding predicts that anti-NKG2A may further enhance the antitumor effects occurring from UV-oHSV2 stimulation, and that anti-HLA-E treatment also has this possibility ( 118 ).…”

Section: Molecular Mechanisms By Which Different Oncolytic Virus Ther...mentioning

confidence: 98%

“…HSV not only acts through type I IFNs with NK cells, but also mediates type II IFNs stimulation of NK cells. Recent studies have shown that UV-oHSV2 can stimulate NK cells to secrete IFN-γ, which is achieved through the Toll-like receptor 2 (TLR2)/NF-κB signaling pathway, which activates multiple immune cells to exert anti-tumor responses ( 118 ). Furthermore, UV-oHSV2 stimulation promoted the expression of two checkpoint molecules, one located on NK cells, NKG2A, and the other on tumor cells, HLA-E.…”

Section: Molecular Mechanisms By Which Different Oncolytic Virus Ther...mentioning

confidence: 99%

The gamble between oncolytic virus therapy and IFN

Tan

Wang

et al. 2022

Front. Immunol.

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Various studies are being conducted on oncolytic virotherapy which one of the mechanisms is mediating interferon (IFN) production by it exerts antitumor effects. The antiviral effect of IFN itself has a negative impact on the inhibition of oncolytic virus or tumor eradication. Therefore, it is very critical to understand the mechanism of IFN regulation by oncolytic viruses, and to define its mechanism is of great significance for improving the antitumor effect of oncolytic viruses. This review focuses on the regulatory mechanisms of IFNs by various oncolytic viruses and their combination therapies. In addition, the exerting and the producing pathways of IFNs are briefly summarized, and some current issues are put forward.

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“…For the first time, it was discovered that UV-oHSV2 activation increases the expression of two checkpoint molecules, NKG2A (on NK cells) and HLA-E (on tumor cells). Treatment with anti-NKG2A and anti-HLA-E might improve the anticancer effects of UV-oHSV2-stimulated NK92 cells both in vitro and in vivo ( 146 ). Ma et al.…”

Section: Dcs and Nk Cells As The Enhancer Of Ovsmentioning

confidence: 99%

Dendritic cells and natural killer cells: The road to a successful oncolytic virotherapy

et al. 2023

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Every type of cancer tissue is theoretically more vulnerable to viral infection. This natural proclivity has been harnessed as a new anti-cancer therapy by employing oncolytic viruses (OVs) to selectively infect and destroy cancer cells while providing little or no harm with no toxicity to the host. Whereas the primary oncolytic capabilities of OVs initially sparked the greatest concern, the predominant focus of research is on the association between OVs and the host immune system. Numerous OVs are potent causal agents of class I MHC pathway-related chemicals, enabling early tumor/viral immune recognition and cytokine-mediated response. The modified OVs have been studied for their ability to bind to dendritic cells (DCs) by expressing growth factors, chemokines, cytokines, and defensins inside the viral genome. OVs, like reovirus, can directly infect DCs, causing them to release chemokines and cytokines that attract and excite natural killer (NK) cells. In addition, OVs can directly alter cancer cells’ sensitivity to NK by altering the expression levels of NK cell activators and inhibitors on cancerous cells. Therefore, NK cells and DCs in modulating the therapeutic response should be considered when developing and improving future OV-based therapeutics, whether modified to express transgenes or used in combination with other drugs/immunotherapies. Concerning the close relationship between NK cells and DCs in the potential of OVs to kill tumor cells, we explore how DCs and NK cells in tumor microenvironment affect oncolytic virotherapy and summarize additional information about the interaction mentioned above in detail in this work.

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NK cell tumor therapy modulated by UV-inactivated oncolytic herpes simplex virus type 2 and checkpoint inhibitors

Cited by 19 publications

References 42 publications

Oncolytic adenovirus serotype 35 mediated tumor growth suppressionviaefficient activation and tumor infiltration of natural killer cells

Oncolytic adenovirus serotype 35 mediated tumor growth suppressionviaefficient activation and tumor infiltration of natural killer cells

The gamble between oncolytic virus therapy and IFN

Dendritic cells and natural killer cells: The road to a successful oncolytic virotherapy

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