In situ recruitment of antigen-presenting cells by intratumoral GM-CSF gene delivery

Ping Ying Pan, Yu Li, Qingsheng Li, Pedi Gu, Olivier Martinet, Swan Thung, Shu Hsia Chen

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Proper antigen presentation is paramount to the induction of effective and persistent antitumor immune responses. In a murine model of hepatic metastasis of colon cancer, we found that the numbers of in situ mature dendritic cells (DCs) and macrophages in tumor-infiltrating leukocytes (TILs) were significantly increased in mice treated with the combination therapy of herpes simplex virus thymidine kinase, interleukin 2, and GM-CSF genes when compared with control groups without GM-CSF treatment. Significantly higher levels of IFN-γ, MIP-1α, mIL-12, and GM-CSF were detected in the tumor after the combination therapy. T cells isolated from the combination therapy-treated mice exhibited higher ex vivo direct CTL activity than those from other treatment groups. Antigen-presenting cells (APCs) enriched from the TILs and liver of the combination therapy-treated mice induced higher levels of proliferation by the splenocytes from long-term surviving mice that had been cured of tumors at early time points (days 4 and 7) whereas significant APC activity was only observed in the spleen at the latter time point (day 7, 14) after the combination therapy. In contrast, APCs isolated from tk or tk + IL-2-treated mice did not induce any significant proliferation. Subcutaneous injection of fluorescence-labeled latex microspheres followed by the combination therapy showed a similar sequential trafficking of microspheres, day 4 after the combination therapy to tumor and day 14 to spleen. The results suggest that APCs recruited by intratumoral gene delivery of GM-CSF can capture antigens, mature to a stage suitable for antigen presentation, and subsequently migrate to the spleen where they can efficiently stimulate antigen-specific T cells.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalCancer Immunology, Immunotherapy
Issue number1
StatePublished - Jan 2004


  • Antigen-presenting cell
  • CTL response
  • GM-CSF
  • Migration
  • Spleen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research


Dive into the research topics of 'In situ recruitment of antigen-presenting cells by intratumoral GM-CSF gene delivery'. Together they form a unique fingerprint.

Cite this