Age-associated impairment of antitumor immunity in carcinoma-bearing mice and restoration by oral administration of Lentinula edodes mycelia extract.
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.
Department of Immunology, Shimane University Faculty of Medicine, Izumo, Shimane, 693-8501, Japan.|Central R & D Laboratory, Kobayashi Pharmaceutical Co., Ltd., Ibaragi, Osaka, Japan.
Satoru
S
Ishikawa
Central R & D Laboratory, Kobayashi Pharmaceutical Co., Ltd., Ibaragi, Osaka, Japan.
Yasunori
Y
Matsui
Central R & D Laboratory, Kobayashi Pharmaceutical Co., Ltd., Ibaragi, Osaka, Japan.
Satoshi
S
Wachi
Central R & D Laboratory, Kobayashi Pharmaceutical Co., Ltd., Ibaragi, Osaka, Japan.
Hiroshi
H
Yamaguchi
Department of Immunology, Shimane University Faculty of Medicine, Izumo, Shimane, 693-8501, Japan.
Nanae
N
Harashima
Department of Immunology, Shimane University Faculty of Medicine, Izumo, Shimane, 693-8501, Japan. haramamo@med.shimane-u.ac.jp.
Mamoru
M
Harada
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020942:Shiitake Mushrooms / Q000378:metabolism / Q000627:therapeutic use*
Aging; IL-6; Inflammation; MDSC; T cell immunity