Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma

Xiuyun Lin; Tao Zeng; Jiani Xiong; Qiong Zhang; Pan Jiang; Xiufeng Li; Shuchun Lin; Qianqian Xu; Huanjiao Weng; Haichun Lai; Huichun Gong; Jinxiang Lin; Niangmei Cheng; Xinling Tian; Yunlu Xu; Shubin Fang; Rong Jin; Zhiwei Chen; Jianbo Yang; Luke Morton; Bevan Yueh; Jizhen Lin

doi:10.1080/15384047.2018.1550569

Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma

Xiuyun Lin, Tao Zeng, Jiani Xiong, Qiong Zhang, Pan Jiang, Xiufeng Li, Shuchun Lin, Qianqian Xu, Huanjiao Weng, Haichun Lai, Huichun Gong, Jinxiang Lin, Niangmei Cheng, Xinling Tian, Yunlu Xu, Shubin Fang, Rong Jin, Zhiwei Chen, Jianbo Yang, Luke MortonBevan Yueh, Jizhen Lin

Research output: Contribution to journal › Article › peer-review

Abstract

The programmed death (PD) pathway is frequently present in the tumor microenvironment (TME) and suppresses tumor immunity by inhibiting the activity of tumor-infiltrating lymphocytes (TILs), particularly, CD8 ⁺ lymphocytes. PD immunotherapy involves stimulation of the immune response in the region surrounding the tumor but is insufficient to prevent tumor progression. Therefore, in this study, we examined the effects of combined PD immunotherapy with fractionated radiotherapy (RT) on antitumor immunity and tumor growth in lymphoma. The immune cell profiles of the TME, blood, and secondary lymphoid organs were determined 7 days after treatment. Four combination therapies were compared. The synergistic effects of αPD-1 mAb and fractionated RT on increased CD8 ⁺ lymphocytes in the TME, blood, and secondary lymphoid organs led to substantial tumor regression in mouse EL4 lymphoma, both locally and systemically. Fractionated RT for 4 days followed by αPD-1 mAb therapy was significantly superior to other schemes in terms of overall survival rates and curative rates in xenograft model mice. Our data indicated that substantial immune responses occurred following combination therapy with fractionated RT and αPD-1 mAb immunotherapy. Our findings provide important insights into the use of RT plus αPD-1 mAb as an efficacious combinatorial therapy.

Original language	English (US)
Pages (from-to)	666-679
Number of pages	14
Journal	Cancer Biology and Therapy
Volume	20
Issue number	5
DOIs	https://doi.org/10.1080/15384047.2018.1550569
State	Published - May 4 2019

Bibliographical note

Funding Information:
This study was supported by the Foundation of National science and technology project record (Grant 2016L301); the Foundation of Colleges and universities industry-academic cooperation projects of Fujian Province (Grant 2017Y41010050); the Foundation of Science and technology platform construction project of Fujian Province (Grants 2015Y2102 and 2014Y2101);The Foundation of national science and technology project record [Grant 2016L301];The Foundation of science and technology platform construction project of Fujian province [Grants 2015Y2102 and 2014Y2101];The Foundation of colleges and universities industry-academic cooperation project of Fujian province [Grant 2017Y41010050].

Funding Information:
This study was supported by the Foundation of National science and technology project record (Grant 2016L301); the Foundation of Colleges and universities industry-academic cooperation projects of Fujian Province (Grant 2017Y41010050); the Foundation of Science and technology platform construction project of Fujian Province (Grants 2015Y2102 and 2014Y2101);The Foundation of national science and technology project record [Grant 2016L301];The Foundation of science and technology platform construction project of Fujian province [Grants 2015Y2102 and 2014Y2101];The Foundation of colleges and universities industry-academic cooperation project of Fujian province [Grant 2017Y41010050]. We are particularly grateful to Dr. Lieping Chen (Yale University, New Haven, CT USA) and Liqun Luo (Fujian Medical University, Fuzhou, China) for their gift of ?PD-1 mAb.

Publisher Copyright:
© 2018, © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

antitumor immunity
fractionated radiotherapy
programmed death ligand-1
programmed death-1
scheme

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/15384047.2018.1550569

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Lin, X., Zeng, T., Xiong, J., Zhang, Q., Jiang, P., Li, X., Lin, S., Xu, Q., Weng, H., Lai, H., Gong, H., Lin, J., Cheng, N., Tian, X., Xu, Y., Fang, S., Jin, R., Chen, Z., Yang, J., ... Lin, J. (2019). Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma. Cancer Biology and Therapy, 20(5), 666-679. https://doi.org/10.1080/15384047.2018.1550569

Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma. / Lin, Xiuyun; Zeng, Tao; Xiong, Jiani; Zhang, Qiong; Jiang, Pan; Li, Xiufeng; Lin, Shuchun; Xu, Qianqian; Weng, Huanjiao; Lai, Haichun; Gong, Huichun; Lin, Jinxiang; Cheng, Niangmei; Tian, Xinling; Xu, Yunlu; Fang, Shubin; Jin, Rong; Chen, Zhiwei; Yang, Jianbo; Morton, Luke; Yueh, Bevan ; Lin, Jizhen.

In: Cancer Biology and Therapy, Vol. 20, No. 5, 04.05.2019, p. 666-679.

Research output: Contribution to journal › Article › peer-review

Lin, X, Zeng, T, Xiong, J, Zhang, Q, Jiang, P, Li, X, Lin, S, Xu, Q, Weng, H, Lai, H, Gong, H, Lin, J, Cheng, N, Tian, X, Xu, Y, Fang, S, Jin, R, Chen, Z, Yang, J, Morton, L, Yueh, B & Lin, J 2019, 'Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma', Cancer Biology and Therapy, vol. 20, no. 5, pp. 666-679. https://doi.org/10.1080/15384047.2018.1550569

Lin, Xiuyun ; Zeng, Tao ; Xiong, Jiani ; Zhang, Qiong ; Jiang, Pan ; Li, Xiufeng ; Lin, Shuchun ; Xu, Qianqian ; Weng, Huanjiao ; Lai, Haichun ; Gong, Huichun ; Lin, Jinxiang ; Cheng, Niangmei ; Tian, Xinling ; Xu, Yunlu ; Fang, Shubin ; Jin, Rong ; Chen, Zhiwei ; Yang, Jianbo ; Morton, Luke ; Yueh, Bevan ; Lin, Jizhen. / Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma. In: Cancer Biology and Therapy. 2019 ; Vol. 20, No. 5. pp. 666-679.

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title = "Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma",

abstract = " The programmed death (PD) pathway is frequently present in the tumor microenvironment (TME) and suppresses tumor immunity by inhibiting the activity of tumor-infiltrating lymphocytes (TILs), particularly, CD8 + lymphocytes. PD immunotherapy involves stimulation of the immune response in the region surrounding the tumor but is insufficient to prevent tumor progression. Therefore, in this study, we examined the effects of combined PD immunotherapy with fractionated radiotherapy (RT) on antitumor immunity and tumor growth in lymphoma. The immune cell profiles of the TME, blood, and secondary lymphoid organs were determined 7 days after treatment. Four combination therapies were compared. The synergistic effects of αPD-1 mAb and fractionated RT on increased CD8 + lymphocytes in the TME, blood, and secondary lymphoid organs led to substantial tumor regression in mouse EL4 lymphoma, both locally and systemically. Fractionated RT for 4 days followed by αPD-1 mAb therapy was significantly superior to other schemes in terms of overall survival rates and curative rates in xenograft model mice. Our data indicated that substantial immune responses occurred following combination therapy with fractionated RT and αPD-1 mAb immunotherapy. Our findings provide important insights into the use of RT plus αPD-1 mAb as an efficacious combinatorial therapy. ",

keywords = "antitumor immunity, fractionated radiotherapy, programmed death ligand-1, programmed death-1, scheme",

author = "Xiuyun Lin and Tao Zeng and Jiani Xiong and Qiong Zhang and Pan Jiang and Xiufeng Li and Shuchun Lin and Qianqian Xu and Huanjiao Weng and Haichun Lai and Huichun Gong and Jinxiang Lin and Niangmei Cheng and Xinling Tian and Yunlu Xu and Shubin Fang and Rong Jin and Zhiwei Chen and Jianbo Yang and Luke Morton and Bevan Yueh and Jizhen Lin",

note = "Funding Information: This study was supported by the Foundation of National science and technology project record (Grant 2016L301); the Foundation of Colleges and universities industry-academic cooperation projects of Fujian Province (Grant 2017Y41010050); the Foundation of Science and technology platform construction project of Fujian Province (Grants 2015Y2102 and 2014Y2101);The Foundation of national science and technology project record [Grant 2016L301];The Foundation of science and technology platform construction project of Fujian province [Grants 2015Y2102 and 2014Y2101];The Foundation of colleges and universities industry-academic cooperation project of Fujian province [Grant 2017Y41010050]. Funding Information: This study was supported by the Foundation of National science and technology project record (Grant 2016L301); the Foundation of Colleges and universities industry-academic cooperation projects of Fujian Province (Grant 2017Y41010050); the Foundation of Science and technology platform construction project of Fujian Province (Grants 2015Y2102 and 2014Y2101);The Foundation of national science and technology project record [Grant 2016L301];The Foundation of science and technology platform construction project of Fujian province [Grants 2015Y2102 and 2014Y2101];The Foundation of colleges and universities industry-academic cooperation project of Fujian province [Grant 2017Y41010050]. We are particularly grateful to Dr. Lieping Chen (Yale University, New Haven, CT USA) and Liqun Luo (Fujian Medical University, Fuzhou, China) for their gift of ?PD-1 mAb. Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018 The Author(s). Published with license by Taylor & Francis Group, LLC.",

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doi = "10.1080/15384047.2018.1550569",

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AU - Lin, Xiuyun

AU - Zeng, Tao

AU - Xiong, Jiani

AU - Zhang, Qiong

AU - Jiang, Pan

AU - Li, Xiufeng

AU - Lin, Shuchun

AU - Xu, Qianqian

AU - Weng, Huanjiao

AU - Lai, Haichun

AU - Gong, Huichun

AU - Lin, Jinxiang

AU - Cheng, Niangmei

AU - Tian, Xinling

AU - Xu, Yunlu

AU - Fang, Shubin

AU - Jin, Rong

AU - Chen, Zhiwei

AU - Yang, Jianbo

AU - Morton, Luke

AU - Yueh, Bevan

AU - Lin, Jizhen

N1 - Funding Information: This study was supported by the Foundation of National science and technology project record (Grant 2016L301); the Foundation of Colleges and universities industry-academic cooperation projects of Fujian Province (Grant 2017Y41010050); the Foundation of Science and technology platform construction project of Fujian Province (Grants 2015Y2102 and 2014Y2101);The Foundation of national science and technology project record [Grant 2016L301];The Foundation of science and technology platform construction project of Fujian province [Grants 2015Y2102 and 2014Y2101];The Foundation of colleges and universities industry-academic cooperation project of Fujian province [Grant 2017Y41010050]. Funding Information: This study was supported by the Foundation of National science and technology project record (Grant 2016L301); the Foundation of Colleges and universities industry-academic cooperation projects of Fujian Province (Grant 2017Y41010050); the Foundation of Science and technology platform construction project of Fujian Province (Grants 2015Y2102 and 2014Y2101);The Foundation of national science and technology project record [Grant 2016L301];The Foundation of science and technology platform construction project of Fujian province [Grants 2015Y2102 and 2014Y2101];The Foundation of colleges and universities industry-academic cooperation project of Fujian province [Grant 2017Y41010050]. We are particularly grateful to Dr. Lieping Chen (Yale University, New Haven, CT USA) and Liqun Luo (Fujian Medical University, Fuzhou, China) for their gift of ?PD-1 mAb. Publisher Copyright: © 2018, © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC.

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N2 - The programmed death (PD) pathway is frequently present in the tumor microenvironment (TME) and suppresses tumor immunity by inhibiting the activity of tumor-infiltrating lymphocytes (TILs), particularly, CD8 + lymphocytes. PD immunotherapy involves stimulation of the immune response in the region surrounding the tumor but is insufficient to prevent tumor progression. Therefore, in this study, we examined the effects of combined PD immunotherapy with fractionated radiotherapy (RT) on antitumor immunity and tumor growth in lymphoma. The immune cell profiles of the TME, blood, and secondary lymphoid organs were determined 7 days after treatment. Four combination therapies were compared. The synergistic effects of αPD-1 mAb and fractionated RT on increased CD8 + lymphocytes in the TME, blood, and secondary lymphoid organs led to substantial tumor regression in mouse EL4 lymphoma, both locally and systemically. Fractionated RT for 4 days followed by αPD-1 mAb therapy was significantly superior to other schemes in terms of overall survival rates and curative rates in xenograft model mice. Our data indicated that substantial immune responses occurred following combination therapy with fractionated RT and αPD-1 mAb immunotherapy. Our findings provide important insights into the use of RT plus αPD-1 mAb as an efficacious combinatorial therapy.

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KW - fractionated radiotherapy

KW - programmed death ligand-1

KW - programmed death-1

KW - scheme

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Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma

Abstract

Bibliographical note

Keywords

UN SDGs

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