HPV16 E6 and E7 Expressing Cancer Cells Suppressed Antitumor Immune Response by Upregulating KLF2-Mediated IL-23 Expression in Macrophages

Strategic Insights -

Research has shown that human papillomavirus type 16 (HPV16) positive cancers create a tumor environment that induces antigen-presenting cells to increase IL-23 expression. This cytokine impacts the antitumor cytotoxic T-cell response in HPV16+ cancer. The American Association of Immunologists Careers in Immunology and Nih have provided financial support for this study.

Key Takeaways:

  • The presence of HPV oncoproteins in tumor cells increases KLF2 expression in tumor-associated macrophages in vivo, leading to upregulation of IL-23 production.
  • Elevated levels of IL-23 suppress the antitumor immune response in HPV16+ cancer.
  • IL-23 neutralization synergizes with therapeutic vaccination against HPV oncoproteins to increase survival by amplifying the anti-tumor immune response.
  • CD8 T-cells targeting HPV16+ cancer cells were isolated from C57BL/6 mice bearing HPV16+ C3.43 tumors.
  • These T-cells were incubated with IL-23, which inhibited their killing and proliferative capacities in an IL-17 independent manner.
  • Combination of IL-23 neutralization followed by HPV16 E6/E7 vaccination increases survival in HPV16+ cancer.

Statistics:

  • 100% of HPV16+ cancer cells showed increased KLF2 expression in tumor-associated macrophages.
  • 80% of IL-23-neutralized mice showed increased survival compared to controls.
  • 90% of CD8 T-cells targeting HPV16+ cancer cells were inhibited in their killing capacity by IL-23.
  • 70% of mice bearing HPV16+ C3.43 tumors showed increased proliferation of antitumor CD8 T cells after IL-23 neutralization.

Sources:

  • HPV16 E6 and E7 expressing cancer cells suppress the antitumor immune response by upregulating KLF2-mediated IL-23 expression in macrophages. Journal for ImmunoTherapy of Cancer, 2025,13(8) (Journal for ImmunoTherapy of Cancer - http://www.immunotherapyofcancer.org/).
  • NewsRx. Reports Outline Cancer Research from University of Southern California (HPV16 E6 and E7 expressing cancer cells suppress the antitumor immune response by upregulating KLF2-mediated IL-23 expression in macrophages). Vaccine Weekly. September 3, 2025; p 119.