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 | |
| State | Published - May 4 2019 |
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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 journal › Article
}
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 -