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

Abstract

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.

Advances in cell-based delivery of oncolytic viruses as therapy for lung cancer

“…Although DCs can preferentially move to tumor areas, they have a relatively limited inherent capacity to destroy tumor cells. 173 , 174 However, as with other OVs, the fast generation of neutralizing antibodies poses a significant challenge to effective systemic administration. Therefore, the capacity of T cells, DCs, and peripheral blood mononuclear cells (PBMCs) as some types of CCs was evaluated, in how far they could shield reovirus and myxoma virus from systemic neutralization 41 , 42 , 94 ( Table 2 ).…”

Euonymus alatus (Thunb.) Siebold leaf extract enhanced immunostimulatory effects in a cyclophosphamide-induced immunosuppressed rat model

“…NK cells play an important role in the initial immune response and can target and kill virus-infected cells and cancer cells. It is also activated by the stimulation of cytokines and chemokines and is one of the methods that can lead to the activation of innate and adaptive immune cells ( 38 , 39 ). Our results showed that the EA-treated group had significantly increased NK cell activity.…”

“…Our results showed that the EA-treated group had significantly increased NK cell activity. According to a previous report, NK cells are activated by IFN- or macrophage-derived cytokines, and by recognizing changes in major histocompatibility complex (MHC) class expression and blocking the activation of non-infected cells, only infected cells selectively induce apoptosis ( 39 ). In this result, EA may play an effective role in activating NK cells to clear cells infected with viruses and bacteria and may enhance cell-mediated immune responses.…”

Metabolic regulation of tumor-associated macrophage heterogeneity: insights into the tumor microenvironment and immunotherapeutic opportunities

“…The tumor microenvironment (TME), an intricate assembly of nonmalignant cellular entities, vascular structures, and extracellular components, plays a cardinal role in facilitating tumor progression, metastasis, and invasion [1,2]. Its immunological profile, marked by a high prevalence of tumor-associated macrophages (TAMs), has been associated with the prognosis of patients, cementing the integral role of the TAMs in the tumor milieu [3][4][5][6]. With TAMs playing diverse roles in tumor biology, understanding their composition can illuminate the complex dynamics of tumor progression, enhance predictive accuracy regarding disease outcomes, and inform the development of innovative anti-cancer strategies.…”