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

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

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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, …

Cancer biology & therapy, Vol.20(5), pp.666-679

05/04/2019

DOI: 10.1080/15384047.2018.1550569

PMCID: PMC6605991

PMID: 30572778

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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.

antitumor immunity

fractionated radiotherapy

programmed death ligand-1

programmed death-1

scheme

Details

Title: Subtitle: Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma
Creators: Xiuyun Lin - Union Hospital
Tao Zeng - Immunotherapy Research and Development, CreMab Biopharma, Inc
Jiani Xiong - Fujian Medical University
Qiong Zhang - Fujian Medical University
Pan Jiang - Fujian Medical University
Xiufeng Li - Immunotherapy Research and Development, CreMab Biopharma, Inc
Shuchun Lin - Union Hospital
Qianqian Xu - Immunotherapy Research and Development, CreMab Biopharma, Inc
Huanjiao Weng - Immunotherapy Research and Development, CreMab Biopharma, Inc
Haichun Lai - Union Hospital
Huichun Gong - Immunotherapy Research and Development, CreMab Biopharma, Inc
Jinxiang Lin - Immunotherapy Research and Development, CreMab Biopharma, Inc
Niangmei Cheng - Fujian Medical University
Xinling Tian - Immunotherapy Research and Development, CreMab Biopharma, Inc
Yunlu Xu - Fujian Medical University
Shubin Fang - Fujian Medical University
Rong Jin - Immunotherapy Research and Development, CreMab Biopharma, Inc
Zhiwei Chen - Fuzhou University
Jianbo Yang - University of Minnesota
Luke Morton - University of Minnesota
Bevan Yueh - University of Minnesota
Jizhen Lin - University of Minnesota
Resource Type: Journal article
Publication Details: Cancer biology & therapy, Vol.20(5), pp.666-679
DOI: 10.1080/15384047.2018.1550569
PMID: 30572778
PMCID: PMC6605991
NLM abbreviation: Cancer Biol Ther
ISSN: 1538-4047
eISSN: 1555-8576
Publisher: Taylor & Francis
Number of pages: 14
Grant note: Grant 2016L301 / The Foundation of national science and technology project record Grants 2015Y2102 and 2014Y2101 / The Foundation of science and technology platform construction project of Fujian province Grant 2017Y41010050 / The Foundation of colleges and universities industry-academic cooperation project of Fujian province
Language: English
Date published: 05/04/2019
Academic Unit: Otolaryngology
Record Identifier: 9984966850502771

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