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01.02.2008 | Original Article

Immunotherapy with dendritic cells pulsed with tumor-derived gp96 against murine lung cancer is effective through immune response of CD8⁺ cytotoxic T lymphocytes and natural killer cells

verfasst von: Naofumi Shinagawa, Koichi Yamazaki, Yasuaki Tamura, Akihito Imai, Eiki Kikuchi, Hiroshi Yokouchi, Fumihiro Hommura, Satoshi Oizumi, Masaharu Nishimura

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 2/2008

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Abstract

Background and purpose

Immunization with heat shock proteins, gp96, elicits specific protective immunity against parent tumors. However, it is marginally effective as a therapeutic tool against established tumors. In the present study, we evaluated the efficacy and mechanism of immunotherapy with bone marrow-derived dendritic cells (DCs) pulsed with tumor-derived gp96 against murine lung cancer.

Methods

Mice were transplanted subcutaneously with ovalbumin (OVA)-transfected Lewis Lung Cancer (LLC-OVA) cells and immunized with gp96 derived from LLC-OVA, DCs, or DCs pulsed with gp96 derived from LLC-OVA.

Results

The antitumor effect was significantly enhanced in the mice immunized with DCs pulsed with gp96 derived from LLC-OVA, compared to mice immunized with gp96 or DCs (P < 0.05). The antitumor effect was significantly dependent on natural killer (NK) cells and CD8⁺ cells and partially dependent on CD4⁺ cells. Analysis by laser confocal microscopy demonstrated that gp96 was shown on the cell surface at 15 min, and after 30 min internalized in the endosomes and not in the endoplasmic reticulum or lysosomes. OVA-specific⁺ CD8⁺ cells were more readily recruited into the draining lymph nodes and higher CD8⁺ cytotoxic T cell activity against LLC-OVA was observed in splenocytes from mice immunized with DCs pulsed with gp96 derived from LLC-OVA. Re-challenge of the surviving mice with LLC-OVA tumors after the initial tumor inoculation showed dramatic retardation in tumor growth.

Conclusion

In conclusion, immunotherapy of DCs pulsed with tumor-derived gp96 against murine lung cancer is effective through immune response of CD8⁺ cytotoxic T lymphocytes and NK cells.

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Titel: Immunotherapy with dendritic cells pulsed with tumor-derived gp96 against murine lung cancer is effective through immune response of CD8+ cytotoxic T lymphocytes and natural killer cells
verfasst von: Naofumi Shinagawa
Koichi Yamazaki
Yasuaki Tamura
Akihito Imai
Eiki Kikuchi
Hiroshi Yokouchi
Fumihiro Hommura
Satoshi Oizumi
Masaharu Nishimura
Publikationsdatum: 01.02.2008
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 2/2008
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0359-3

Neu im Fachgebiet Onkologie

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Springer Medizin

Immunotherapy with dendritic cells pulsed with tumor-derived gp96 against murine lung cancer is effective through immune response of CD8⁺ cytotoxic T lymphocytes and natural killer cells

Abstract

Background and purpose

Methods

Results

Conclusion

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Springer Medizin

Abstract

Background and purpose

Methods

Results

Conclusion

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