Dendritic cell-based vaccines suppress metastatic liver tumor via activation of local innate and acquired immunity.

Abstract

BACKGROUND:

Dendritic cell (DC)-based vaccines have been applied clinically in the setting of cancer, but tumor-associated antigens (TAAs) have not yet been enough identified in various cancers. In this study, we investigated whether preventive vaccination with unpulsed DCs or peptide-pulsed DCs could offer anti-tumor effects against MC38 or BL6 liver tumors.

METHODS:

Mice were subcutaneously (s.c.) immunized with unpulsed DCs or the recently defined TAA EphA2 derived peptide-pulsed dendritic cells (Eph-DCs) to treat EphA2-positive MC38 and EphA2-negative BL6 liver tumors. Liver mononuclear cells (LMNCs) from treated mice were subjected to (51)Cr release assays against YAC-1 target cells. In some experiments, mice were injected with anti-CD8, anti-CD4 or anti-asialo GM1 antibody to deplete each lymphocyte subsets.

RESULTS:

Immunization with unpulsed DCs displayed comparable efficacy against both MC38 and BL6 liver tumors when compared with Eph-DCs. Both DC-based vaccines significantly augmented the cytotoxicity of LMNCs against YAC-1 cells. In vivo antibody depletion studies revealed that NK cells, as well as, CD4+ and CD8+ T cells play critical roles in the anti-tumor efficacy associated with either DC-based modality. Tumor-specific cytotoxic T lymphocyte (CTL) activity was generally higher if mice had received Eph-DCs versus unpulsed DCs. Importantly, the mice that had been protected from MC38 liver tumor by either unpulsed DCs or Eph-DCs became resistant to s.c. MC38 rechallenge, but not to BL6 rechallenge.

CONCLUSIONS:

These results demonstrate that unpulsed DC vaccines might serve as an effective therapy for treating metastatic liver tumor, for which TAA has not yet been identified.

• Authors: Shinjiro Yamaguchi, Tomohide Tatsumi, Tetsuo Takehara, Akira Sasakawa, Hayato Hikita, Keisuke Kohga, Akio Uemura, Ryotaro Sakamori, Kazuyoshi Ohkawa, Norio Hayashi
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 57 Issue 12 Pg. 1861-9 (Dec 2008) ISSN: 0340-7004 [Print] Germany
• PMID: 18438665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• Receptor, EphA2

Topics

• Animals
• Antigens, Neoplasm (immunology)
• Cancer Vaccines (immunology, therapeutic use)
• Dendritic Cells (immunology, transplantation)
• Female
• Flow Cytometry
• Immunity, Innate
• Killer Cells, Natural (immunology)
• Liver Neoplasms (immunology, therapy)
• Lymphocytes (immunology)
• Mice
• Receptor, EphA2 (immunology)