Inducing multiple antibodies to treat squamous cell esophageal carcinoma
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RESEARCH ARTICLE
Open Access
Inducing multiple antibodies to treat squamous cell esophageal carcinoma Isamu Hoshino1* , Yoshihiro Nabeya1, Nobuhiro Takiguchi1, Hisashi Gunji1, Fumitaka Ishige2, Yosuke Iwatate2, Akiko Kuwajima3, Fumiaki Shiratori1,4, Rei Okada4 and Hideaki Shimada4
Abstract Background: The positive response and the clinical usefulness of 14 serum antibodies in patients with esophageal squamous cell carcinoma (ESCC) were examined in this study. The Cancer Genome Atlas (TCGA) was used to investigate the frequency of gene expressions, mutations, and amplification of these 14 antigens and also the possible effects of antibody induction. Methods: Blood serum derived from 85 patients with ESCC was collected and analyzed for the 14 antibodies using ELISA. The prognosis between positive and negative antibodies were then compared. The antibody panel included LGALS1, HCA25a, HCC-22-5, and HSP70. Results: Patient serum was positive for all antibodies, except VEGF, with the positive rates ranging from 1.18 to 10.59%. Positive rates for LGALS1, HCA25a, HCC-22-5, and HSP70 were > 10%. TCGA data revealed that all antigenrelated genes had little or no mutation or amplification, and hence an increase in gene expression affected antibody induction. The positive results from the panel accounted for the positive rate comparable to the combination of CEA and SCC. No significant association was observed between the presence of antibodies and disease prognosis. Conclusions: The detection rates of LGALS1, HCA25a, HCC-22-5, and HSP70 were 10% higher in patients with ESCC. Gene overexpression may be involved in such antibody production. These four antibodies were applied as a panel in comparison with conventional tumor markers. Moreover, it was confirmed that the combination of this panel and the conventional tumor markers significantly improved the positive rate. Keywords: Autoantibody, Esophageal squamous cell carcinoma, TCGA
Background Drugs that block immune checkpoints such as PD-1, PDL1, and CTLA-4 have been developed in recent years [1, 2]. They have a significant effect on highly malignant cancers and are used effectively in cancer treatment. The principle underlying their mechanism of action is based on the appearance of cancer antigens that present cancer cell components on the basis of abnormal expression [1, * Correspondence: [email protected] 1 Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba 260-8717, Japan Full list of author information is available at the end of the article
3]. T cells recognize the antigens present on the surface of cancer cells and begin attacking cancer cells [4]. The appearance of neoantigens and cancer antigens specific to cancer cells is believed to result from genetic mutations and gene expression abnormalities due to genetic instability [1, 5, 6]. Neoantigens and cancer antigens are recognized as foreign substances by the body, leading to a robust T-cell response. Recent research has reported about the possibility of correlating th
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