Human papillomavirus-driven immune deviation: challenge and novel opportunity for immunotherapy

Area of Science:

• Immunology
• Oncology
• Virology

Background:

• Human papillomavirus (HPV)-associated cancers pose a significant clinical challenge.
• HPV oncogene expression drives cancer development but can compromise the innate immune system early on.
• This immune compromise facilitates viral persistence and cancer progression.

Purpose of the Study:

• To explore the immune system's role in controlling HPV-associated neoplastic processes.
• To identify strategies for immune targeting of HPV oncogene expression.
• To understand how to overcome immune suppressive microenvironments in HPV-driven cancers.

Main Methods:

• Review of immune system interactions during HPV oncogenesis.
• Analysis of immune suppressive mechanisms mediated by viral oncogenes (E6/E7).
• Evaluation of therapeutic vaccine strategies and combination treatments.

Main Results:

• High-risk HPV infection leads to immune suppression via antigen-presenting cell loss and altered chemokine/cytokine responses.
• An immunosuppressive microenvironment is established with increased Tregs, Th17, MDSCs, and PD-L1.
• Overexpressed E6/E7 compromises DNA repair, leading to genomic instability and immune escape.
• Early-phase trials show promise for therapeutic HPV vaccines in high-grade lesions.

Conclusions:

• Therapeutic vaccines targeting HPV oncogenes are a promising strategy.
• Overcoming local and systemic immune suppression is crucial for advanced disease.
• Combination therapies involving TLR stimulation, IL-6 pathway inhibition, immune-checkpoint inhibition, and modulation of Tregs, MDSCs, and macrophages could enhance anti-tumor immunity.
• Future success depends on well-designed, combination immunotherapy protocols.