Naringin promotes cancer immunity by inducing cross-presentation by antigen-presenting cells.
5 affiliations
- 1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan.
- 2Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan.
- 3Department of Pathology, Sapporo Medical University, Sapporo, Hokkaido, Japan.
- 4Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan. [email protected].
- 5Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto, Japan. [email protected].
Abstract
Successful immune checkpoint inhibitor (ICI) treatment of cancer requires adequate infiltration of cytotoxic CD8+T lymphocytes (CTLs) in tumors. Previous studies have identified the compound naringin, which increases CTL infiltration and rescues ICI efficacy in CTL-lacking tumors, and cancer CTL priming has been shown to rely on antigen cross-presentation (XPT). Therefore, the present study aimed to examine the effect of naringin on XPT by various human and murine antigen-presenting cells (APCs). The results indicated that naringin increases XPT by XPT-competent APCs, including murine bone marrow (BM) dendritic cells, peritoneal macrophages (MΦs), and human monocyte-derived dendritic cells (HMDCs). However, XPT was not observed with BM- or human monocyte-derived MΦs with or without naringin. Naringin reduced the activity of lysosomes, suppressing the degradation of internalized antigens, thereby increasing antigen cytosolic escape and MHC class I molecule-presenting antigens. In addition, human lymph node (LN) sinus MΦs were transcriptomically more similar to XPT-competent HMDCs than other LN MΦ groups. Taken together, these data suggest that naringin promotes XPT by XPT-competent APCs, which may explain why naringin was found to promote cancer immunity in our previous studies. This finding highlights the potential for developing cancer immunotherapies that induce XPT, offering a promising strategy to enhance antitumor immune responses.
Related
- Pimozide enhances antigen cross-presentation and promotes cytotoxic CD8+ T cell immunity by stimulating dendritic cells
- Stimulate-and-retain hydrogel strategy integrating oncolytic virus and oxaliplatin for dual ICD-inducing antitumor immunity.
- SEC31A promotes gastric cancer progression by inducing the PI3K/AKT/mTOR pathway and enhancing the CCL5-mediated M2 polarization and recruitment of tumor-associated macrophages
- Human CD4 T cells coordinate antitumor immunity through indirect antigen presentation
- Microbial adhesion promotes Piezo1 activation to initiate innate immunity
BibTeX
@article{pan2026naringin,
title = {{Naringin promotes cancer immunity by inducing cross-presentation by antigen-presenting cells.}},
author = {Cheng Pan and Yukio Fujiwara and Daiki Yoshii and Jiahao Pan and Takuya Shiota and Yuko Miyasato and Yuka Mizue and Yoshihiko Hirohashi and Yoshihiro Komohara},
journal = {Cancer immunology, immunotherapy : CII},
year = {2026},
month = jul,
doi = {10.1007/s00262-026-04497-7},
url = {https://europepmc.org/article/MED/42907578},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Naringin promotes cancer immunity by inducing cross-presentation by antigen-presenting cells.
AU - Cheng Pan
AU - Yukio Fujiwara
AU - Daiki Yoshii
AU - Jiahao Pan
AU - Takuya Shiota
AU - Yuko Miyasato
AU - Yuka Mizue
AU - Yoshihiko Hirohashi
AU - Yoshihiro Komohara
PY - 2026
DA - 2026/07/01
JO - Cancer immunology, immunotherapy : CII
DO - 10.1007/s00262-026-04497-7
UR - https://europepmc.org/article/MED/42907578
AB - Successful immune checkpoint inhibitor (ICI) treatment of cancer requires adequate infiltration of cytotoxic CD8+T lymphocytes (CTLs) in tumors. Previous studies have identified the compound naringin, which increases CTL infiltration and rescues ICI efficacy in CTL-lacking tumors, and cancer CTL priming has been shown to rely on antigen cross-presentation (XPT). Therefore, the present study aimed to examine the effect of naringin on XPT by various human and murine antigen-presenting cells (APCs). The results indicated that naringin increases XPT by XPT-competent APCs, including murine bone marrow (BM) dendritic cells, peritoneal macrophages (MΦs), and human monocyte-derived dendritic cells (HMDCs). However, XPT was not observed with BM- or human monocyte-derived MΦs with or without naringin. Naringin reduced the activity of lysosomes, suppressing the degradation of internalized antigens, thereby increasing antigen cytosolic escape and MHC class I molecule-presenting antigens. In addition, human lymph node (LN) sinus MΦs were transcriptomically more similar to XPT-competent HMDCs than other LN MΦ groups. Taken together, these data suggest that naringin promotes XPT by XPT-competent APCs, which may explain why naringin was found to promote cancer immunity in our previous studies. This finding highlights the potential for developing cancer immunotherapies that induce XPT, offering a promising strategy to enhance antitumor immune responses.
SN - 0340-7004
SN - 1432-0851
ER -