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 journalArticle

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 languageEnglish (US)
Pages (from-to)666-679
Number of pages14
JournalCancer Biology and Therapy
Volume20
Issue number5
DOIs
StatePublished - May 4 2019

Fingerprint

Lymphoma
Radiotherapy
Monoclonal Antibodies
Growth
Tumor Microenvironment
Neoplasms
Immunotherapy
Immunity
Lymphocytes
Tumor-Infiltrating Lymphocytes
Therapeutics
Heterografts

Keywords

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

Cite this

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 journalArticle

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.
@article{4a827491912a4c9982509bfaa38faa16,
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",
year = "2019",
month = "5",
day = "4",
doi = "10.1080/15384047.2018.1550569",
language = "English (US)",
volume = "20",
pages = "666--679",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "5",

}

TY - JOUR

T1 - Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma

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

PY - 2019/5/4

Y1 - 2019/5/4

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.

AB - 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.

KW - antitumor immunity

KW - fractionated radiotherapy

KW - programmed death ligand-1

KW - programmed death-1

KW - scheme

UR - http://www.scopus.com/inward/record.url?scp=85059000365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059000365&partnerID=8YFLogxK

U2 - 10.1080/15384047.2018.1550569

DO - 10.1080/15384047.2018.1550569

M3 - Article

C2 - 30572778

AN - SCOPUS:85059000365

VL - 20

SP - 666

EP - 679

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 5

ER -