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Age-associated impairment of antitumor immunity in carcinoma-bearing mice and restoration by oral administration of Lentinula edodes mycelia extract

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Abstract

Because cancer is associated with aging, immunological features in the aged should be considered in anticancer immunotherapy. In this study, we investigated antitumor immunity in aged mice using a CT26 colon carcinoma model. The tumor growth of CT26 was accelerated in aged mice compared with that in young mice, but this difference was not observed in nude mice. The serum levels of IL-6 and TNF-α were higher in aged mice than those in young mice, irrespective of the CT26-bearing state. The in vitro induction of CT26-specific CTLs from aged mice that were vaccinated with doxorubicin (DTX)-treated CT26 cells was impaired. In vivo neutralization of IL-6, but not TNF-α, showed a tendency to restore the in vitro induction of CT26-specific CTLs from vaccinated aged mice. Analyses on tumor-infiltrating immune cells as early as day 5 after CT26 inoculation revealed that monocytic and granulocytic MDSCs preferentially infiltrated into tumor sites in aged mice compared with young mice. Alternatively, oral administration of Lentinula edodes mycelia (L.E.M.) extract, which has the potential to suppress inflammation in tumor-bearing hosts, decreased the serum levels of IL-6 in aged mice. When administration of L.E.M. extract was started 1 week earlier, CT26 growth was retarded in aged mice and the in vivo priming of tumor-specific CTLs was improved in CT26-vaccinated aged mice. These results indicate early infiltration of MDSCs is related to impaired immunity of aged hosts and that oral administration of L.E.M. extract can mitigate the impairment.

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Abbreviations

DTX:

Doxorubicin

L.E.M.:

Lentinus edodes mycelia

Th1:

Type I helper

Treg:

Regulatory T cell

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Acknowledgments

The authors are grateful to Ms. Tamami Moritani for her technical assistance. This study was supported in part by JSPS KAKENHI Grant (No. 25430150 to N. Harashima, and No. 24501331 to M. Harada) and from the Shimane University “SUIGANN” Project.

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Authors and Affiliations

  1. Department of Immunology, Shimane University Faculty of Medicine, Izumo, Shimane, 693-8501, Japan

    Satoru Ishikawa, Nanae Harashima & Mamoru Harada

  2. Central R & D Laboratory, Kobayashi Pharmaceutical Co., Ltd., Ibaragi, Osaka, Japan

    Satoru Ishikawa, Yasunori Matsui, Satoshi Wachi & Hiroshi Yamaguchi

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  1. Satoru Ishikawa
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  2. Yasunori Matsui
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  3. Satoshi Wachi
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  4. Hiroshi Yamaguchi
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Correspondence to Mamoru Harada.

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Mamoru Harada received donations for research from the Kobayashi Pharmaceutical Co., Ltd. All other authors declare that they have no conflict of interest.

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Ishikawa, S., Matsui, Y., Wachi, S. et al. Age-associated impairment of antitumor immunity in carcinoma-bearing mice and restoration by oral administration of Lentinula edodes mycelia extract. Cancer Immunol Immunother 65, 961–972 (2016). https://doi.org/10.1007/s00262-016-1857-y

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  • DOI: https://doi.org/10.1007/s00262-016-1857-y

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