Integrity of plasma DNA is inversely correlated with vaccine-induced antitumor immunity in ovarian cancer patients
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ORIGINAL ARTICLE
Integrity of plasma DNA is inversely correlated with vaccine‑induced antitumor immunity in ovarian cancer patients Kayoko Waki1 · Kanako Yokomizo1 · Kouichiro Kawano2 · Naotake Tsuda2 · Nobukazu Komatsu3 · Akira Yamada1 Received: 9 January 2020 / Accepted: 28 April 2020 © The Author(s) 2020
Abstract Cancer immunotherapy including vaccine therapy is a promising modality for cancer treatment, but few patients show its clinical benefits currently. The identification of biomarkers that can identify patients who will benefit from cancer immunotherapy is thus important. Here, we investigated the potential utility of the circulating cell-free DNA (cfDNA) integrity—a ratio of necrotic cell-derived, longer DNA fragments versus apoptotic cell-derived shorter fragments of Alu gene—as a biomarker of vaccine therapy for patients with ovarian cancer. We analyzed plasma samples from 39 patients with advanced or recurrent ovarian cancer enrolled in clinical trials for personalized peptide vaccinations. We observed that (1) the cfDNA integrity was decreased after the first cycle of vaccination, and (2) the decreased levels of cfDNA integrity were correlated with vaccine-induced immune responses; i.e., decreased cfDNA integrity was observed in 91.7% and 59.3% of the IgGpositive and negative patients, respectively (p = 0.0445). Similarly, decreased cfDNA integrity was observed in 92.9% and 56.0% of CTL response-positive and negative patients, respectively (p = 0.0283). These results suggest that the circulating cfDNA integrity is a possible biomarker for cancer vaccine therapy. Keywords CTL · DNA integrity · IgG · Ovarian cancer · Peptide vaccine
Introduction Ovarian cancer is the eighth most common cancer in women, and each year worldwide, nearly 300,000 women newly develop ovarian cancer and 185,000 individuals die from it [1]. Taxane and platinum-based chemotherapy and/or bevacizumab (an anti-angiogenic molecular targeting agent) are widely used to treat ovarian cancer [2]. The presence of tumor-infiltrated T lymphocytes and the expression of cytotoxic T-lymphocyte (CTL)-directed tumor antigens in ovarian cancer tissues have been reported [3–5], which suggests that immunotherapy could become a promising modality for the treatment of ovarian cancer. * Akira Yamada [email protected]‑u.ac.jp 1
Cancer Vaccine Development Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Fukuoka 830‑0011, Japan
2
Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
3
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
We have conducted clinical studies of a peptide-based cancer vaccine in patients with advanced or recurrent ovarian cancer [6]. The cancer vaccine consisted of 31 CTLepitope peptides, and a maximum of four peptides was selected from among the 31 peptides based on each patient’s HLA-A locus types and pre-vaccination immunity to the peptides; we thus refer to it as the "personalized pepti
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