干旱区生态环境知识资源中心(Arid): Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention

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DOI	10.1158/2326-6066.CIR-19-0253
	Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention
	Omene, Coral 1; Ma, Lin 2; Moore, Jade 2; Ouyang, Haoxu 3; Illa-Bochaca, Irineu 3; Chou, William 2; Patel, Manan S.3; Sebastiano, Christopher 3; Demaria, Sandra 3,5; Mao, Jian-Hua 4; Karagoz, Kubra 1; Gatza, Michael L.1; Barcellos-Hoff, Mary Helen 2
通讯作者	Barcellos-Hoff, Mary Helen
来源期刊	CANCER IMMUNOLOGY RESEARCH
ISSN	2326-6066
EISSN	2326-6074
出版年	2020
卷号	8 期号:2 页码:217-229
英文摘要	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 g-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 TGFb. 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.
类型	Article
语种	英语
国家	USA
开放获取类型	Green Submitted, Green Accepted
收录类别	SCI-E
WOS记录号	WOS:000510418700007
WOS关键词	ACID PHENETHYL ESTER ; BREAST-CANCER ; IONIZING-RADIATION ; PRECLINICAL MODELS ; T-CELLS ; GENE ; MICROENVIRONMENT ; EXPRESSION ; RADIOTHERAPY ; INFLAMMATION
WOS类目	Oncology ; Immunology
WOS研究方向	Oncology ; Immunology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/314212
作者单位	1.Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ USA; 2.Univ Calif San Francisco, San Francisco, CA 94143 USA; 3.NYU, Sch Med, New York, NY USA; 4.Lawrence Berkeley Natl Lab, Berkeley, CA USA; 5.Weill Cornell Med Coll, New York, NY USA
推荐引用方式 GB/T 7714	Omene, Coral,Ma, Lin,Moore, Jade,et al. Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention[J],2020,8(2):217-229.
APA	Omene, Coral.,Ma, Lin.,Moore, Jade.,Ouyang, Haoxu.,Illa-Bochaca, Irineu.,...&Barcellos-Hoff, Mary Helen.(2020).Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention.CANCER IMMUNOLOGY RESEARCH,8(2),217-229.
MLA	Omene, Coral,et al."Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention".CANCER IMMUNOLOGY RESEARCH 8.2(2020):217-229.