TLR9 acts as a sensor for tumor-released DNA to modulate anti-tumor immunity after chemotherapy

Tae Heung Kang, Chih Ping Mao, Young Seob Kim, Tae Woo Kim, Andrew Yang, Brandon Lam, Ssu Hsueh Tseng, Emily Farmer, Yeong Min Park, Chien Fu Hung

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


The tumor microenvironment exists in a state of dynamic equilibrium, in which a balance of agonist and antagonist signals govern the anti-tumor immune responses. Previous studies have shown that chemotherapy could shift this balance in favor of agonistic signals for the anti-tumor immune responses mounted by CD8+ cytotoxic T lymphocytes (CTL), providing sufficiently high antigen density within the tumor. We undertook the current study to characterize the anti-tumor immune response following chemotherapy and its underlying mechanisms. We show that this 'adjuvant effect' of chemotherapy is, at least partially, mediated by the release of tumor DNA and acts through the Toll-like receptor 9 (TLR9) pathway. We found that tumor-released DNA causes accumulation, antigen uptake, and maturation of dendritic cells (DCs) in the tumor in a TLR9-dependent manner. These DCs subsequently migrate into the draining lymph nodes and prime tumor-specific CTLs. Our study provides novel insights to the molecular and cellular mechanisms by which chemotherapy converts the tumor microenvironment into a site permissive for the activation of a potent tumor-specific adaptive immune response.

Original languageEnglish
Article number260
JournalJournal for ImmunoTherapy of Cancer
Issue number1
Publication statusPublished - 2019 Oct 16

Bibliographical note

Funding Information:
This work was supported by the American Cancer Society grant RSG-07-199-01-LIB, NIH/NCI P50 CA098252, NIH/NCI P50 CA96784, NIH/NCI R01 CA233486. This work was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (NRF-2016R1A5A2012284, NRF-2017R1A2A1A17069818, and NRF-2018R1A2B6008455). This study was also supported by a grant from Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2524). Brandon Lam is a recipient of the Ruth L. Kirschstein National Research Service Award (F31 CA236051).

Publisher Copyright:
© 2019 The Author(s).


  • Chemotherapy
  • Toll-like receptor 9
  • Tumor DNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


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