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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Understanding the interplay between oHSV and the host immune system: Implications for therapeutic oncolytic virus
Kalkidan Ayele1, Hiroaki Wakimoto2, Hans J Nauwynck3
1Department of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USA.
Abstract:
Oncolytic herpes simplex viruses (oHSV) preferentially replicate in cancer cells while inducing antitumor immunity, and thus, they are often referred to as in situ cancer vaccines. OHSV infection of tumors elicits diverse host immune responses comprising both innate and adaptive components. Although the innate and adaptive immune responses primarily target the tumor, they also contribute to antiviral immunity, limiting viral replication/oncolysis. OHSV-encoded proteins use various mechanisms to evade host antiviral pathways and immune recognition, favoring oHSV replication, oncolysis, and spread. In general, oHSV infection and replication within tumors results in a series of sequential events, such as oncolysis and release of tumor and viral antigens, dendritic cell-mediated antigen presentation, T cell priming and activation, T cell trafficking and infiltration to tumors, and T cell recognition of cancer cells, leading to tumor (and viral) clearance. These sequential events align with all steps of the cancer-immunity cycle. However, a comprehensive understanding of the interplay between oHSV and host immune responses is crucial to optimize oHSV-induced antitumor immunity and efficacy. Therefore, this review aims to elucidate oHSV's communication with innate and adaptive immune systems and use such interactions to improve oHSV's potential as a potent immunovirotherapeutic agent against cancer.
Insights
Oncolytic herpes simplex viruses (oHSV) act as in situ cancer vaccines by replicating in tumors and triggering immune responses. Understanding oHSV-host interactions is key to enhancing its cancer immunotherapy potential.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Oncolytic herpes simplex viruses (oHSV) selectively infect and replicate within cancer cells, acting as in situ cancer vaccines.
- oHSV infection initiates both innate and adaptive immune responses, which can target tumor cells but also limit viral activity.
- oHSV proteins possess mechanisms to evade host antiviral defenses, promoting viral replication and tumor lysis.
Purpose of the Study:
- To review the complex interplay between oHSV and host immune systems.
- To elucidate how oHSV communicates with innate and adaptive immunity.
- To optimize oHSV-based immunovirotherapies for improved cancer treatment efficacy.
Main Methods:
- Literature review of oHSV mechanisms and host immune responses.
- Analysis of sequential events in oHSV-induced antitumor immunity.
- Synthesis of information on immune evasion strategies employed by oHSV.
Main Results:
- oHSV infection triggers a cascade of events aligning with the cancer-immunity cycle, including antigen release, immune cell priming, and tumor cell recognition.
- Host immune responses, while beneficial for tumor clearance, can also restrict oHSV replication.
- oHSV utilizes immune evasion strategies to enhance its oncolytic and immunotherapeutic potential.
Conclusions:
- A thorough understanding of oHSV-immune system interactions is critical for maximizing its therapeutic efficacy.
- Leveraging these interactions can improve oHSV's role as a potent immunovirotherapeutic agent.
- Further research into optimizing oHSV immunovirotherapy is warranted for effective cancer treatment.
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