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Androgen Signaling Contributes to Sex Differences in Cancer by Inhibiting NF-κB Activation in T Cells and Suppressing Antitumor Immunity.
Zhang, Xiaomin; Cheng, Limin; Gao, Chengqi; Chen, Jing; Liao, Shuangye; Zheng, Yongqiang; Xu, Liping; He, Jingjing; Wang, Danyang; Fang, Ziqian; Zhang, Jianeng; Yan, Min; Luan, Yi; Chen, Siyu; Chen, Likun; Xia, Xiaojun; Deng, Chunhao; Chen, Guokai; Li, Wende; Liu, Zexian; Zhou, Penghui.
Afiliación
  • Zhang X; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Cheng L; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Gao C; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Chen J; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Liao S; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Zheng Y; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Xu L; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • He J; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Wang D; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Fang Z; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Zhang J; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Yan M; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Luan Y; Department of Pathology, The first Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • Chen S; Department of Clinical Laboratory, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
  • Chen L; Guangdong Laboratory Animals Monitoring Institute, Guangdong Key Laboratory of Laboratory Animals, Guangzhou, China.
  • Xia X; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Deng C; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • Chen G; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China.
  • Li W; Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China.
  • Liu Z; Guangdong Laboratory Animals Monitoring Institute, Guangdong Key Laboratory of Laboratory Animals, Guangzhou, China.
  • Zhou P; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Cancer Res ; 83(6): 906-921, 2023 03 15.
Article en En | MEDLINE | ID: mdl-36634207
Sex is known to be an important factor in the incidence, progression, and outcome of cancer. A better understanding of the underlying mechanisms could help improve cancer prevention and treatment. Here, we demonstrated a crucial role of antitumor immunity in the sex differences in cancer. Consistent with observations in human cancers, male mice showed accelerated tumor progression compared with females, but these differences were not observed in immunodeficient mice. Androgen signaling suppressed T-cell immunity against cancer in males. Mechanistically, androgen-activated androgen receptor upregulated expression of USP18, which inhibited TAK1 phosphorylation and the subsequent activation of NF-κB in antitumor T cells. Reduction of testosterone synthesis by surgical castration or using the small-molecular inhibitor abiraterone significantly enhanced the antitumor activity of T cells in male mice and improved the efficacy of anti-PD-1 immunotherapy. Together, this study revealed a novel mechanism contributing to sex differences in cancer. These results indicate that inhibition of androgen signaling is a promising approach to improve the efficacy of immunotherapy in males. SIGNIFICANCE: Androgen signaling induces immunosuppression in cancer by blocking T-cell activity through upregulation of USP18 and subsequent inhibition of NF-κB activity, providing a targetable axis to improve antitumor immunity in males.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: FN-kappa B / Neoplasias de la Próstata Resistentes a la Castración Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Res Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: FN-kappa B / Neoplasias de la Próstata Resistentes a la Castración Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Res Año: 2023 Tipo del documento: Article País de afiliación: China