Cancer immunotherapy employing an innovative strategy to enhance CD4T cell help in the tumor microenvironment

Liwen Song, Ming Chieh Yang, Jayne Knoff, Tzyy Choou Wu, Chien-Fu Hung, Thorbald Van Hall

Research output: Contribution to journalArticle

Abstract

Chemotherapy and/or radiation therapy are widely used as cancer treatments, but the antitumor effects they produce can be enhanced when combined with immunotherapies. Chemotherapy kills tumor cells, but it also releases tumor antigen and allows the cross-presentation of the tumor antigen to trigger antigenspecific cell-mediated immune responses. Promoting CD4+T helper cell immune responses can be used to enhance the cross-presentation of the tumor antigen following chemotherapy. The pan HLA-DR binding epitope (PADRE peptide) is capable of generating antigen-specific CD4+T cells that bind various MHC class II molecules with high affinity and has been widely used in conjunction with vaccines to improve their potency by enhancing CD4+T cell responses. Here, we investigated whether intratumoral injection of PADRE and the adjuvant CpG into HPV16 E7-expressing TC-1 tumors following cisplatin chemotherapy could lead to potent antitumor effects and antigen-specific cell-mediated immune responses. We observed that treatment with all three agents produced the most potent antitumor effects compared to pairwise combinations. Moreover, treatment with cisplatin, CpG and PADRE was able to control tumors at a distant site, indicating that our approach is able to induce cross-presentation of the tumor antigen. Treatment with cisplatin, CpG and PADRE also enhanced the generation of PADRE-specific CD4+ T cells and E7-specific CD8+T cells and decreased the number of MDSCs in tumor loci. The treatment regimen presented here represents a universal approach to cancer control.

Original languageEnglish (US)
Article numbere115711
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 22 2014

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Tumor Microenvironment
Chemotherapy
T-cells
immunotherapy
Neoplasm Antigens
Immunotherapy
Tumors
Cross-Priming
Cisplatin
neoplasms
antigens
T-Lymphocytes
Drug Therapy
T-lymphocytes
Neoplasms
cisplatin
drug therapy
cells
Antigens
Oncology

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cancer immunotherapy employing an innovative strategy to enhance CD4T cell help in the tumor microenvironment. / Song, Liwen; Yang, Ming Chieh; Knoff, Jayne; Wu, Tzyy Choou; Hung, Chien-Fu; Van Hall, Thorbald.

In: PLoS One, Vol. 9, No. 12, e115711, 22.12.2014.

Research output: Contribution to journalArticle

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