Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity
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 und...
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Frontiers Media S.A.
2021-08-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.733246/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Juan Yang Juan Yang Xianzhi Yang Wenfeng Pan Mingshuo Wang Yuxiong Lu Yuxiong Lu Jianeng Zhang Ziqian Fang Xiaomin Zhang Yin Ji Jin-Xin Bei Jin-Xin Bei Jiajun Dong Yi Wu Chaoyun Pan Guangli Yu Guangli Yu Penghui Zhou Bo Li Bo Li Bo Li |
spellingShingle |
Juan Yang Juan Yang Xianzhi Yang Wenfeng Pan Mingshuo Wang Yuxiong Lu Yuxiong Lu Jianeng Zhang Ziqian Fang Xiaomin Zhang Yin Ji Jin-Xin Bei Jin-Xin Bei Jiajun Dong Yi Wu Chaoyun Pan Guangli Yu Guangli Yu Penghui Zhou Bo Li Bo Li Bo Li Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity Frontiers in Cell and Developmental Biology natural product fucoidan immunotherapy cancer T cells |
author_facet |
Juan Yang Juan Yang Xianzhi Yang Wenfeng Pan Mingshuo Wang Yuxiong Lu Yuxiong Lu Jianeng Zhang Ziqian Fang Xiaomin Zhang Yin Ji Jin-Xin Bei Jin-Xin Bei Jiajun Dong Yi Wu Chaoyun Pan Guangli Yu Guangli Yu Penghui Zhou Bo Li Bo Li Bo Li |
author_sort |
Juan Yang |
title |
Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity |
title_short |
Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity |
title_full |
Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity |
title_fullStr |
Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity |
title_full_unstemmed |
Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor Immunity |
title_sort |
fucoidan-supplemented diet potentiates immune checkpoint blockage by enhancing antitumor immunity |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-08-01 |
description |
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. |
topic |
natural product fucoidan immunotherapy cancer T cells |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.733246/full |
work_keys_str_mv |
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doaj-8adb953937bb492888cc4b0ed8938c722021-08-09T06:53:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.733246733246Fucoidan-Supplemented Diet Potentiates Immune Checkpoint Blockage by Enhancing Antitumor ImmunityJuan Yang0Juan Yang1Xianzhi Yang2Wenfeng Pan3Mingshuo Wang4Yuxiong Lu5Yuxiong Lu6Jianeng Zhang7Ziqian Fang8Xiaomin Zhang9Yin Ji10Jin-Xin Bei11Jin-Xin Bei12Jiajun Dong13Yi Wu14Chaoyun Pan15Guangli Yu16Guangli Yu17Penghui Zhou18Bo Li19Bo Li20Bo Li21Jiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, ChinaJiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, ChinaJiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, ChinaJiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, ChinaClinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, ChinaState Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Diagnostics Co., Ltd., Jiangsu, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, ChinaCenter for Precision Medicine, Sun Yat-sen University, Guangdong, ChinaJiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, ChinaJiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, ChinaJiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, ChinaKey Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Shandong, ChinaLaboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Shandong, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, ChinaJiangmen Central Hospital, Affiliated Jiangmen Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangdong, ChinaCenter for Precision Medicine, Sun Yat-sen University, Guangdong, ChinaImmune 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.733246/fullnatural productfucoidanimmunotherapycancerT cells |