ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCell Models and Preclinical Validation of Immune-Mediating Biological TherapiesView all 6 articles
Enhancing cDC1-mediated anti-tumor immunity limits tumor progression and potentiates anti-PD-1 therapy in intrahepatic cholangiocarcinoma
Provisionally accepted
- Second Xiangya Hospital, Central South University, Changsha, China
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
Purpose: Conventional type 1 dendritic cells (cDC1s) mastermind anti-cancer immunity and play a pivotal role in determining the efficacy of cancer immunotherapies. In this study, we sought to decipher the dynamic changes in the tumor immune landscape during intrahepatic cholangiocarcinoma (iCCA) development and harness the therapeutic potential of targeting cDC1s for cancer therapy. Methods: We constructed spontaneous murine iCCAs via hydrodynamic tail vein injection (HDTVi) of plasmids encoding AKT/YAP. To characterize tumor-infiltrating immune cell populations throughout iCCA carcinogenesis and progression, we performed time-of-flight mass cytometry (CyTOF). To expand and activate cDC1s, we combined Flt3L with poly I:C (FL-pIC) therapy and assessed its therapeutic efficacy in both AKT/YAP-induced iCCAs and a subcutaneous tumor injection model. Flow cytometric analyses were used to evaluate intra-tumoral infiltration levels of cDCs and CD8+ T cells. Results: CyTOF analysis revealed the progressive formation of an immunosuppressive tumor microenvironment as iCCA advances. Crucially, infiltration of cDC1s dramatically decreases in advanced iCCAs compared to early-stage tumors. Combined FL-pIC therapy preferentially expanded CD103+ cDC1s, powerfully inhibiting tumorigenesis in AKT/YAP-driven murine iCCAs and sensitizing these tumors to anti-PD-1 therapy. Moreover, FL-pIC therapy markedly suppressed the growth of established mIC-23 subcutaneous tumors. 删除[孙宝业]: This is a provisional file, not the final typeset article Conclusions: Our findings demonstrate that recruiting and activating intra-tumoral cDC1s is feasible and essential for driving anti-tumor CD8+ T cell immune responses and enhancing anti-PD-1 therapeutic effectiveness in iCCA.
Keywords: intrahepatic cholangiocarcinoma, Tumor Microenvironment, Immune Evasion, Anti-PD-1 Therapy, Conventional dendritic cells
Received: 19 Sep 2025; Accepted: 26 Nov 2025.
Copyright: © 2025 Pei, Song, Zhou, Shu, Huang, Li, Dai and Sun. 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: Bao-Ye Sun
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.