Low CD86 expression is a predictive biomarker for clinical response to the therapeutic human papillomavirus vaccine IGMKK16E7: results of a post hoc analysis.

IF 3.4 Q2 ONCOLOGY
Hanano Ando, Yuki Katoh, Osamu Kobayashi, Yuji Ikeda, Hideaki Yahata, Takashi Iwata, Toyomi Satoh, Azusa Akiyama, Daichi Maeda, Yumiko Hori-Hirose, Yukari Uemura, Kaori Nakayama-Hosoya, Kanoko Katoh, Takahiro Nakajima, Ayumi Taguchi, Atsushi Komatsu, Saki Kamata, Naoko Tomita, Kiyoko Kato, Daisuke Aoki, Shizunobu Igimi, Ai Kawana-Tachikawa, Danny J Schust, Kei Kawana
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引用次数: 0

Abstract

Background: Although therapeutic human papillomavirus vaccines could offer a noninvasive treatment for patients with cervical intraepithelial neoplasia, none has been clinically implemented. Oral administration of the therapeutic human papillomavirus vaccine IGMKK16E7 results in the histological regression of human papillomavirus 16-positive cervical intraepithelial neoplasia 2/3 to normal (complete response). We investigated biomarkers that could predict complete response after oral administration of IGMKK16E7.

Methods: Forty-two patients administered high-dose oral IGMKK16E7 in a phase I/II trial were included. Cervix-exfoliated cells were collected before vaccine administration. Gene expression of CD4, CD8, FOXP3, programmed cell death 1 protein, CTLA4, CD103, CD28, CD80, CD86, and programmed cell death 1 ligand 1 in the cells was measured by quantitative reverse transcriptase-polymerase chain reaction. Receiver operating characteristic 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.

Results: The only predictive biomarker of vaccine response for which receiver operating characteristic curve analysis showed significant diagnostic performance with histological complete response was CD86 (area under the curve = 0.71, 95% confidence interval = 0.53 to 0.88, P = .020). Patients with complete response had significantly lower CD86 expression (CD86-low) than patients with no complete response (P = .035). The complete response rates for CD86-low and CD86-high patients were 50% and 19%, respectively, and CD86-low patients had a significantly higher complete response rate (P = .047). Compared with all patients, the CD86-low group had a 1.5-fold increase in the complete response rate. Gene expression of CD86 and CTLA4 showed the strongest positive correlation with clinical outcomes in the incomplete response group (P < .001).

Conclusion: Low expression of CD86 in exfoliated cervical cells can be used as a pretreatment biomarker to predict histological complete response after IGMKK16E7 administration.

低 CD86 表达是治疗性 HPV 疫苗 IGMKK16E7 临床反应的预测性生物标志物:事后分析的结果。
背景:尽管治疗性HPV疫苗可为宫颈上皮内瘤变(CIN)患者提供一种非侵入性治疗方法,但目前尚未在临床上应用。口服治疗性 HPV 疫苗 IGMKK16E7 可使 HPV16 阳性 CIN2/3 在组织学上恢复正常(完全应答:CR)。在此,我们研究了可预测口服 IGMKK16E7 后 CR 的生物标志物:在一项 I/II 期试验中,42 例患者接受了大剂量口服 IGMKK16E7。用药前收集宫颈脱落细胞。通过定量 RT-PCR 检测细胞中 CD4、CD8、Foxp3、PD-1、CTLA-4、CD103、CD28、CD80、CD86 和 PD-L1 的基因表达。采用 ROC 曲线分析和 Mann-Whitney 检验来探索潜在的生物标记物。采用皮尔逊相关系数分析将基因表达谱与临床结果相关联:结果:ROC曲线分析显示,唯一能预测疫苗反应的生物标记物是CD86(AUC 0.71,95%XI 0.53-0.88,p = .020),它与组织学CR具有显著的诊断性能。CR 患者的 CD86 表达(CD86-低)明显低于非 CR 患者(p = .035)。CD86-低和CD86-高病例的CR率分别为50%和19%,CD86-低病例的CR率明显更高(p = .047)。与所有患者相比,CD86低组的CR率增加了1.5倍。CD86和CTLA-4的基因表达与非CR组的临床结果呈最强的正相关(p 结论:CD86和CTLA-4的基因表达与非CR组的临床结果呈最强的正相关:脱落宫颈细胞中 CD86 的低表达可作为治疗前的生物标志物,预测使用 IGMKK16E7 后的组织学 CR。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
JNCI Cancer Spectrum
JNCI Cancer Spectrum Medicine-Oncology
CiteScore
7.70
自引率
0.00%
发文量
80
审稿时长
18 weeks
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