ORIGINAL RESEARCH article

Front. Immunol.

Sec. Molecular Innate Immunity

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1543403

Cannabidiol polarizes human neutrophils toward a cancer-promoting phenotype

Provisionally accepted
‪Idan Cohen‬‏‪Idan Cohen‬‏1*Mona KhouryMona Khoury1,2Hong YuxiangHong Yuxiang1,2,3Dayana Blokon-KoganDayana Blokon-Kogan4,5Stela GengrinovitchStela Gengrinovitch1Harel EitamHarel Eitam1Moran Avraham-KelbertMoran Avraham-Kelbert1Hadas Weinstein-MaromHadas Weinstein-Marom4,5Peng XuPeng Xu3Gil Bar-SelaGil Bar-Sela1,2*
  • 1Ha'Emek Medical Center, Afula, Israel
  • 2Department of Immunology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Haifa, Israel
  • 3Guangdong Technion-Israel Institute of Technology (GTIIT), Shantou, Guangdong Province, China
  • 4Migal - Galilee Research Institute, Qiryat Shemona, Israel
  • 5Tel-Hai College, Tel Hai, Northern District, Israel

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

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

Cannabidiol (CBD) is widely used as a natural alternative supplementary treatment for side effects and symptom relief in many diseases. Although the benefits and risks of using CBDs are still largely unknown, consumption has grown constantly. We showed that CBD promotes N2-like cancer supporting neutrophil polarization. Human primary neutrophils exposed to CBD gain N2polarization features, exhibit reduced oxidative burst-induced bacterial killing, and produce cytokine and chemokine arrays similar to N2-polarized cells. CBD-treated neutrophils also rapidly display a landscape of surface markers compatible with the described setup, known for N2polarized cells, and can promote cancer cell proliferation, migration, and angiogenesis. Furthermore, CBD-stimulated neutrophils suppress T-cell proliferation, and the conditioned medium of these cells elevates the expression of PD-L1 in cancer cells, suggesting that this signaling pathway may be involved in regulating T-cell antitumor immunity. Our results underscore the therapeutic potential of CBD and emphasize the need to understand its signaling pathway..

Keywords: Primary neutrophils, Cannabinol (CBD), Neutrophil Activation, Cytokine secretion, NEtosis

Received: 11 Dec 2024; Accepted: 01 Jul 2025.

Copyright: © 2025 Cohen‬‏, Khoury, Yuxiang, Blokon-Kogan, Gengrinovitch, Eitam, Avraham-Kelbert, Weinstein-Marom, Xu and Bar-Sela. 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:
‪Idan Cohen‬‏, Ha'Emek Medical Center, Afula, Israel
Gil Bar-Sela, Department of Immunology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Haifa, Israel

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material