Cancer Relevance of Circulating Antibodies - Against LINE-1 Antigens in Humans

Sep 24, 2026

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Long interspersed nuclear element-1 (LINE-1 or L1) is epigenetically silenced in normal tissues but is frequently derepressed in cancer, making L1-encoded proteins potential tumor-associated antigens. The study developed an immunoassay to detect circulating autoantibodies against L1 proteins in human blood. In over 2,800 individuals, cancer patients showed higher IgG titers against ORF1p and ORF2p, with ORF1p-reactive IgG elevated in stages 1 and 2.

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CategoryHealthcare

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Abstract

Significance

Introduction

RESEARCH ARTICLE [https://doi.org/10.1158/2767-9764.CRC-23-0289](https://doi.org/10.1158/2767-9764.CRC-23-0289) OPEN ACCESS Cancer Relevance of Circulating Antibodies Check for updates Against LINE-1 Antigens in Humans Alexandra V. Vylegzhanina1 , Ivan A. Bespalov1 , Ksenia A. Novototskaya-Vlasova2 , Brandon M. Hall1 , Anatoli S. Gleiberman1 , Han Yu2 , Olga V. Leontieva2 , Katerina I. Leonova2 , Oleg V. Kurnasov3 , Andrei L. Osterman3 , Grace K. Dy2 , Alexey A. Komissarov4 , 5 , Elena Vasilieva4 , 5 , Jeff Gehlhausen6 , Akiko Iwasaki6 , 7 , Christine B. Ambrosone2 , Takemasa Tsuji8 , Junko Matsuzaki8 , Kunle Odunsi8 , Ekaterina L. Andrianova1 , and Andrei V. Gudkov1 , 2 ABSTRACT Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant family of autonomous retrotransposons occupying over 17% of human DNA, is epigenetically silenced in normal tissues by the mechanisms involving p53 but is frequently derepressed in cancer, suggesting that L1-encoded proteins may act as tumor-associated antigens recognized by the immune system. In this study, we established an immunoassay to detect circulating autoantibodies against L1 proteins in human blood. Using this assay in >2,800 individuals with or without cancer, we observed significantly higher IgG titers against L1-encoded ORF1p and ORF2p in patients with lung, pancreatic, ovarian, esophageal, and liver cancers than in healthy individuals. Remarkably, elevated levels of anti–ORF1p-reactive IgG were observed in patients with cancer with disease stages 1 and 2, indicating that the immune response to L1 antigens can occur in the early phases of carcinogenesis. We concluded that the antibody response against L1 antigens could contribute to the diagnosis and determination of immunoreactivity of tumors among cancer types that frequently escape early detection. Significance: The discovery of autoantibodies against antigens encoded by L1 retrotransposons in patients with five poorly curable cancer types has potential implications for the detection of an ongoing carcinogenic process and tumor immunoreactivity. Introduction Long interspersed nuclear element-1 (L1) is a non-long terminal repeat (non-LTR) retrotransposon comprising hundreds of thousands of copies accumulated during mammalian evolution (1) . In humans, approximately halfa million copies of L1 collectively occupy over 17% of the DNA (2) . Most of these sequences are functionally deficient because of truncations, internal rearrangements, and mutations. Only approximately 150 copies of L1 elements 1 Genome Protection, Inc., Buffalo, New York. 2 Roswell Park Comprehensive Cancer Center, Buffalo, New York. 3 Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California. 4 I.V. Davydovsky Clinical City Hospital, Moscow, Russia. 5A. I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia. 6Yale University, New Haven, Connecticut. 7 Howard Hughes Medical Institute, Chevy Chase, Maryland. 8 University of Chicago Medicine Comprehensive Cancer Center, Chicago, Illinois. Corresponding Authors: Andrei V. Gudkov, Roswell Park Comprehensive Cancer Center, Elm and Carlton streets, Buffalo, NY 14263 . E-mail: [andrei.gudkov@roswellpark.org](andrei.gudkov@roswellpark.org); and Ekaterina L. Andrianova, [kandrianova@genomeprotection.com](kandrianova@genomeprotection.com) [doi:](doi: 10.1158/2767-9764.CRC-23-0289)[ 10.1158/2767-9764.CRC-23-0289](doi: 10.1158/2767-9764.CRC-23-0289) This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4 .0) license. © 2023 The Authors; Published by the American Association for Cancer Research are retrotransposition competent in humans (3) . Among these full-length L1s, only a few “hot” loci contribute to bulk L1 mRNA expression (4) . Intact L1 sequences are approximately 6 kb long and encode two polypeptides, ORF1p and ORF2p (5) . ORF1p is an RNA-binding protein (6) and ORF2p is a mul

FAQs

What question does the study address about LINE-1 in cancer?

It investigates whether circulating autoantibodies against LINE-1-encoded proteins are more common in cancer patients and whether this response occurs early in carcinogenesis.

How did the researchers detect antibodies against LINE-1 proteins?

They established an immunoassay to detect circulating autoantibodies against L1 proteins in human blood.

Which cancer types and antibody targets showed higher levels in patients?

Patients with lung, pancreatic, ovarian, esophageal, and liver cancers had significantly higher IgG titers against ORF1p and ORF2p, with elevated anti-ORF1p-reactive IgG also seen in stages 1 and 2.

Sep 24, 2026

Uploaded by Aran