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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1528138
This article is part of the Research Topic Epigenetic Alterations in Tumors and Therapeutic Resistance View all articles

CA19-9-related macrophage polarization drives poor prognosis in HCC after immune checkpoint inhibitor treatment

Provisionally accepted
Tingting Du Tingting Du 1Jialin Zou Jialin Zou 2Yunying Yang Yunying Yang 1Honghui Xie Honghui Xie 3Hui Pang Hui Pang 1Wenquan Zhuang Wenquan Zhuang 1Shutong Wang Shutong Wang 1Guangyan Wei Guangyan Wei 1*
  • 1 The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  • 2 Longgang Central Hospital, Shenzhen, Guangdong Province, China
  • 3 Lingshan County people's Hospital, Lingshan, China

The final, formatted version of the article will be published soon.

    Background: Elevated levels of carbohydrate antigen 19-9 (CA19-9) levels are known to worsen outcomes in various tumors by influencing immune responses.However, the role of CA19-9 in immunotherapy for hepatocellular carcinoma (HCC) remains poorly understood.Methods: This study included 621 patients treated with anti-PD-1/PD-L1 treatment at the First Affiliated Hospital of Sun Yat-sen University from January 2017 to March 2023. During immunotherapy, CA19-9 levels were measured and classified as either elevated (≥35 U/mL) or normal (<35 U/mL) for clinical analysis.Results: Patients with elevated CA19-9 levels had significantly worse progressionfree survival (PFS) and overall survival (OS). The 1-year and 2-year PFS rates were 53.3% and 29.1% in the normal CA19-9 group compared to 16.9% and 11.3% in the elevated group (p < 0.001). Similarly, the 1-year and 2-year OS rates were 90.5% and 75.5% in the normal group versus 64.0% and 36.5% in the elevated group (p < 0.001).Multivariate analysis confirmed CA19-9 was an independent prognostic factor for both PFS and OS. Bioinformatic analysis indicated that FUT3, a key gene in CA19-9 synthesis, correlated with increased macrophage infiltration. And increased M2 macrophage levels and reduced M1 macrophage levels were noted in HCC samples with elevated CA19-9 levels. Further in vivo experiments indicated blocking CA19-9 improved the efficacy of PD-1 treatment through inducing the M1-like polarization of macrophages.Our findings demonstrate that elevated CA19-9 levels during immunotherapy are associated with poor survival outcomes in HCC patients. These findings highlight the crucial role of CA19-9 in shaping the tumor immune environment, particularly through its effect on macrophage polarization, and suggest that targeting CA19-9 may improve immunotherapy outcomes.

    Keywords: HCC1, CA19-92, immunotherapy3, Tumor microenvironment4, Macrophages5

    Received: 18 Nov 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Du, Zou, Yang, Xie, Pang, Zhuang, Wang and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Guangyan Wei, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

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