Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention.

Autor:	Omene C; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey., Ma L; University of California, San Francisco, San Francisco, California., Moore J; University of California, San Francisco, San Francisco, California., Ouyang H; New York University School of Medicine, New York, New York., Illa-Bochaca I; New York University School of Medicine, New York, New York., Chou W; University of California, San Francisco, San Francisco, California., Patel MS; New York University School of Medicine, New York, New York., Sebastiano C; New York University School of Medicine, New York, New York., Demaria S; New York University School of Medicine, New York, New York., Mao JH; Lawrence Berkeley National Laboratory, Berkeley, California., Karagoz K; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey., Gatza ML; Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey., Barcellos-Hoff MH; University of California, San Francisco, San Francisco, California. MaryHelen.Barcellos-Hoff@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2020 Feb; Vol. 8 (2), pp. 217-229. Date of Electronic Publication: 2019 Dec 12.
DOI:	10.1158/2326-6066.CIR-19-0253
Abstrakt:	Because the incidence of breast cancer increases decades after ionizing radiation exposure, aging has been implicated in the evolution of the tumor microenvironment and tumor progression. Here, we investigated radiation-induced carcinogenesis using a model in which the mammary glands of 10-month-old BALB/c mice were transplanted with Trp53 -null mammary tissue 3 days after exposure to low doses of sparsely ionizing γ-radiation or densely ionizing particle radiation. Mammary transplants in aged, irradiated hosts gave rise to significantly more tumors that grew more rapidly than those in sham-irradiated mice, with the most pronounced effects seen in mice irradiated with densely ionizing particle radiation. Tumor transcriptomes identified a characteristic immune signature of these aggressive cancers. Consistent with this, fast-growing tumors exhibited an immunosuppressive tumor microenvironment with few infiltrating lymphocytes, abundant immunosuppressive myeloid cells, and high COX-2 and TGFβ. Only irradiated hosts gave rise to tumors lacking cytotoxic CD8 + lymphocytes (defined here as immune desert), which also occurred in younger irradiated hosts. These data suggest that host irradiation may promote immunosuppression. To test this, young chimera mice were fed chow containing a honeybee-derived compound with anti-inflammatory and immunomodulatory properties, caffeic acid phenethyl ester (CAPE). CAPE prevented the detrimental effects of host irradiation on tumor growth rate, immune signature, and immunosuppression. These data indicated that low-dose radiation, particularly densely ionizing exposure of aged mice, promoted more aggressive cancers by suppressing antitumor immunity. Dietary intervention with a nontoxic immunomodulatory agent could prevent systemic effects of radiation that fuel carcinogenesis, supporting the potential of this strategy for cancer prevention. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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