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Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity.
Yang, Juan; Yang, Xianzhi; Pan, Wenfeng; Wang, Mingshuo; Lu, Yuxiong; Zhang, Jianeng; Fang, Ziqian; Zhang, Xiaomin; Ji, Yin; Bei, Jin-Xin; Dong, Jiajun; Wu, Yi; Pan, Chaoyun; Yu, Guangli; Zhou, Penghui; Li, Bo.
Afiliación
  • Yang J; Jiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
  • Yang X; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, China.
  • Pan W; Jiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
  • Wang M; Jiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
  • Lu Y; Jiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
  • Zhang J; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, China.
  • Fang Z; Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • Zhang X; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, China.
  • Ji Y; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, China.
  • Bei JX; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, China.
  • Dong J; State Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Diagnostics Co., Ltd., Jiangsu, China.
  • Wu Y; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, China.
  • Pan C; Center for Precision Medicine, Sun Yat-sen University, Guangdong, China.
  • Yu G; Jiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
  • Zhou P; Jiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
  • Li B; Jiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
Front Cell Dev Biol ; 9: 733246, 2021.
Article en En | MEDLINE | ID: mdl-34434936
Immune checkpoint blockade (ICB) therapies such as PD-1 antibodies have produced significant clinical responses in treating a variety of human malignancies, yet only a subset of cancer patients benefit from such therapy. To improve the ICB efficacy, combinations with additional therapeutics were under intensive investigation. Recently, special dietary compositions that can lower the cancer risk or inhibit cancer progression have drawn significant attention, although few were reported to show synergistic effects with ICB therapies. Interestingly, Fucoidan is naturally derived from edible brown algae and exhibits antitumor and immunomodulatory activities. Here we discover that fucoidan-supplemented diet significantly improves the antitumor activities of PD-1 antibodies in vivo. Specifically, fucoidan as a dietary ingredient strongly inhibits tumor growth when co-administrated with PD-1 antibodies, which effects can be further strengthened when fucoidan is applied before PD-1 treatments. Immune analysis revealed that fucoidan consistently promotes the activation of tumor-infiltrating CD8+ T cells, which support the evident synergies with ICB therapies. RNAseq analysis suggested that the JAK-STAT pathway is critical for fucoidan to enhance the effector function of CD8+ T cells, which could be otherwise attenuated by disruption of the T-cell receptor (TCR)/CD3 complex on the cell surface. Mechanistically, fucoidan interacts with this complex and augments TCR-mediated signaling that cooperate with the JAK-STAT pathway to stimulate T cell activation. Taken together, we demonstrated that fucoidan is a promising dietary supplement combined with ICB therapies to treat malignancies, and dissected an underappreciated mechanism for fucoidan-elicited immunomodulatory effects in cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Cell Dev Biol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Cell Dev Biol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza