Low CD86 expression is a predictive biomarker for clinical response to the therapeutic HPV vaccine, IGMKK16E7: Results of a post-hoc analysis

• Published in: JNCI cancer spectrum
• Main Authors: Ando, Hanano, Katoh, Yuki, Kobayashi, Osamu, Ikeda, Yuji, Yahata, Hideaki, Iwata, Takashi, Satoh, Toyomi, Akiyama, Azusa, Maeda, Daichi, Hori-Hirose, Yumiko, Uemura, Yukari, Nakayama-Hosoya, Kaori, Katoh, Kanoko, Nakajima, Takahiro, Taguchi, Ayumi, Komatsu, Atsushi, Kamata, Saki, Tomita, Naoko, Kato, Kiyoko, Aoki, Daisuke, Igimi, Shizunobu, Kawana-Tachikawa, Ai, Schust, Danny J, Kawana, Kei
• Format: Journal Article
• Language: English
• Published: England 20.09.2024
• ISSN: 2515-5091

Although therapeutic HPV vaccines could offer a non-invasive treatment for patients with cervical intraepithelial neoplasia (CIN), none have been clinically implemented. Oral administration of the therapeutic HPV vaccine, IGMKK16E7, results in the histological regression of HPV16-positive CIN2/3 to normal (complete response: CR). Here, we investigated biomarkers that could predict CR after oral administration of IGMKK16E7. Forty-two patients administered with high-dose oral IGMKK16E7 in a Phase I/II trial were included. Cervical-exfoliated cells were collected before administration. Gene expression of CD4, CD8, Foxp3, PD-1, CTLA-4, CD103, CD28, CD80, CD86, and PD-L1 in the cells were measured by quantitative RT-PCR. ROC curve analysis and Mann-Whitney tests were used to explore potential biomarkers. Pearson correlation coefficient analysis was used to correlate gene expression profiles with clinical outcome. The only predictive biomarker of vaccine response for which ROC curve analysis showed significant diagnostic performance with histological CR was CD86 (AUC 0.71, 95%XI 0.53-0.88, p = .020). CR patients had significantly lower CD86 expression (CD86-low) than non-CR patients (p = .035). The CR rate for CD86-low and CD86-high cases was 50% and 19%, respectively, and CD86-low cases had a significantly higher CR rate (p = .047). Compared to all patients, the CD86-low group had a 1.5-fold increase in CR rate. Gene expression of CD86 and CTLA-4 showed the strongest positive correlation with clinical outcomes in the non-CR group (p < .001). Low expression of CD86 in exfoliated cervical cells can be used as a pre-treatment biomarker to predict histological CR after IGMKK16E7 use.