Role of MDA5 and interferon-I in dendritic cells for T cell expansion by anti-tumor peptide vaccines in mice

Hussein Sultan, Juan Wu, Takumi Kumai, Andres M. Salazar, Esteban Celis

Research output: Contribution to journalArticle

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Abstract

Cytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role not only in antigen presentation but are critical in generating costimulatory cytokines that promote CTL expansion. Poly-ICLC was shown to be more effective than poly-IC in generating type-I interferon (IFN-I) in various DC subsets, through its enhanced ability to escape the endosomal compartment and stimulate MDA5. In our system, IFN-I did not directly function as a T cell costimulatory cytokine, but enhanced CTL expansion through the induction of IL15. With palmitoylated peptide vaccines, CD8α+ DCs were essential for peptide crosspresentation. For vaccine boosts, non-professional antigen-presenting cells were able to present minimal epitope peptides, but DCs were still required for CTL expansions through the production of IFN-I mediated by poly-ICLC. Overall, these results clarify the roles of DCs, TLR3, MDA5, IFN-I and IL15 in the generation of vast and effective antitumor CTL responses using peptide and poly-IC vaccines.

Original languageEnglish (US)
Pages (from-to)1091-1103
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume67
Issue number7
DOIs
StatePublished - Jul 1 2018

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Melanoma-Specific Antigens
Cancer Vaccines
Subunit Vaccines
Differentiation Antigens
Cytotoxic T-Lymphocytes
Dendritic Cells
Interferons
T-Lymphocytes
Toll-Like Receptor 3
Interleukin-15
Peptides
Vaccines
Cytokines
Neoplasms
Interferon Type I
Antigen Presentation
Antigen-Presenting Cells
Epitopes
Immune System
Immunization

Keywords

  • Dendritic cells
  • Interleukin-15
  • MDA5
  • Peptide vaccines
  • Poly-IC
  • Type-I interferon

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Role of MDA5 and interferon-I in dendritic cells for T cell expansion by anti-tumor peptide vaccines in mice. / Sultan, Hussein; Wu, Juan; Kumai, Takumi; Salazar, Andres M.; Celis, Esteban.

In: Cancer Immunology, Immunotherapy, Vol. 67, No. 7, 01.07.2018, p. 1091-1103.

Research output: Contribution to journalArticle

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