Article Text

Download PDFPDF
EP1165 Induction of chemokine receptor and suppression of inhibitory receptor of CD8 T cell effectively controlled HPV-associated tumor
  1. S Lee and
  2. Y Jung
  1. Seoul St. Mary's Hospital, OBGY, The Catholic University of Korea, Seoul, Republic of Korea


Introduction/Background Activation of exhausted CD8 T cell and migration of immune cells into tumor site is indispensable for overcoming resistance to cancer therapy. We evaluated the role of suppression of inhibitory receptor and chemokine axis in HPV-associated tumor bearing mouse.

Methodology C57BL/6 mice were categorized into four groups according to treatment modality. Mice were challenged with 1×105 TC-1 cells on vulva. HPV DNA therapeutic vaccine was injected intramuscularly and Imiquimod cream was applied on vulva cancer. The mice were harvested on day 21 and immune cells were investigated by flow cytometry. We checked the expression of inhibitory receptors of CD8 T cells, including PD1, TIM3 and LAG3. Chemokine axis such as CXCL9, CXCL10, and CXCR3 were evaluated to demonstrate migration mechanism.

Results Combination of HPV DNA vaccine and Imiquimod resulted in a significantly lowest percentage of inhibitory receptor of CD8+ T cells including PD1, TIM3 and LAG3 in spleen and tumor (p<0.05). They significantly induced accumulation of tumor specific CD8 T cell in tumor site and increased expression of CXCR3 on tumor infiltration CD8 T cell (p<0.05). Chemokine such as CXCL9, CXCL10 was overexpressed in tumor site after combination therapy (p<0.05). Finally, mice treated with combination therapy survived significantly longer than other groups (p<0.05).

Conclusion In conclusion, we overcame T cell exhaustion and identified chemokine axis during migration of CD8 T cell into TC-1 tumor site using HPV DNA vaccine and Imiquimod. This mechanism can be ideal target for future immunotherapy.

Disclosure Nothing to disclose

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.