Low-Dose Gemcitabine Treatment Enhances Immunogenicity and Natural Killer Cell-Driven Tumor Immunity in Lung Cancer

被引：58

作者：

Zhang, Xin ^{[1
]}

Wang, Dong ^{[2
]}

Li, Zhidong ^{[3
]}

Jiao, Defeng ^{[2
]}

Jin, Linlin ^{[2
]}

Cong, Jingjing ^{[2
]}

Zheng, Xiaohu ^{[2
]}

Xu, Lijun ^{[1
]}

机构：

[1] First Hosp Jilin Univ, Dept Resp Med, Changchun, Peoples R China

[2] Univ Sci & Technol China, Sch Life Sci, Div Mol Med, Hefei Natl Lab Phys Sci Microscale,CAS Key Lab In, Hefei, Peoples R China

[3] First Hosp Jilin Univ, Dept Rehabil Med, Changchun, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷

关键词：

low-dose gemcitabine; NK cells; immunogenicity; antitumor immunity; lung cancer; NKG2D LIGANDS; CALRETICULIN EXPOSURE; DANGER SIGNALS; UP-REGULATION; PHASE-III; DEATH; CHEMOTHERAPY; EXPRESSION; CISPLATIN; IMMUNOTHERAPY;

D O I：

10.3389/fimmu.2020.00331

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Gemcitabine has been used as first-line chemotherapy against lung cancer, but many patients experience cancer recurrence. Activation of anti-tumor immunity in vivo has become an important way to prevent recurrence. Anti-tumor immune responses are often dependent upon the immunogenicity of tumors. In our study, we observed that low-dose gemcitabine treatment enhanced the immunogenicity of lung cancer by increasing the exposure of calreticulin, high mobility group box 1, and upregulating expression of NKG2D ligands. Further studies demonstrated that low-dose gemcitabine treatment increased interferon-gamma expression and NK-cell activation in mice. Low-dose gemcitabine treatment was sufficient for inhibiting tumor growth with few side effects in vivo. These data suggest that low-dose gemcitabine-induced immunochemotherapy activated antitumor immunity in immunocompetent patients.

引用

页数：14

共 50 条

[31] Low-dose paclitaxel enhances the anti-tumor efficacy of GM-CSF surface-modified whole-tumor-cell vaccine in mouse model of prostate cancer [J].

He, Qiushan ;

Li, Jinlong ;

Yin, Weihua ;

Song, Zhichun ;

Zhang, Zhen ;

Yi, Tienan ;

Tang, Jia ;

Wu, Demin ;

Lu, Yue ;

Wang, Zhen ;

Liu, Dan ;

Zhang, Xiaoren ;

Hu, Zhiming ;

Gao, Jimin .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2011, 60 (05) :715-730

[32] Low-Dose Apatinib Optimizes Tumor Microenvironment and Potentiates Antitumor Effect of PD-1/PD-L1 Blockade in Lung Cancer [J].

Zhao, Sha ;

Ren, Shengxiang ;

Jiang, Tao ;

Zhu, Bo ;

Li, Xuefei ;

Zhao, Chao ;

Jia, Yijun ;

Shi, Jinpeng ;

Zhang, Limin ;

Liu, Xiaozhen ;

Qiao, Meng ;

Chen, Xiaoxia ;

Su, Chunxia ;

Yu, Hui ;

Zhou, Caicun ;

Zhang, Jun ;

Camidge, D. Ross ;

Hirsch, Fred R. .

CANCER IMMUNOLOGY RESEARCH, 2019, 7 (04) :630-643

[33] PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer [J].

Chabanon, Roman M. ;

Muirhead, Gareth ;

Krastev, Dragomir B. ;

Adam, Julien ;

Morel, Daphne ;

Garrido, Marlene ;

Lamb, Andrew ;

Henon, Clemence ;

Dorvault, Nicolas ;

Rouanne, Mathieu ;

Marlow, Rebecca ;

Bajrami, Ilirjana ;

Cardenosa, Marta Llorca ;

Konde, Asha ;

Besse, Benjamin ;

Ashworth, Alan ;

Pettitt, Stephen J. ;

Haider, Syed ;

Marabelle, Aurelien ;

Tutt, Andrew N. J. ;

Soria, Jean-Charles ;

Lord, Christopher J. ;

Postel-Vinay, Sophie .

JOURNAL OF CLINICAL INVESTIGATION, 2019, 129 (03) :1211-1228

[34] Ad-endostatin treatment combined with low-dose irradiation in a murine lung cancer model [J].

Li, Xiao-Peng ;

Zhang, Hai-Long ;

Wang, Hui-Juan ;

Li, Yong-Xia ;

Li, Meng ;

Lu, Lian ;

Wan, Yang ;

Zhou, Bai-Ling ;

Liu, Yan ;

Pan, Ying ;

Wu, Xiao-Zhe ;

Fan, Ying-Zi ;

Yu, Chao-Heng ;

Wei, Yu-Quan ;

Shi, Hua-Shan .

ONCOLOGY REPORTS, 2014, 32 (02) :650-658

[35] Low-dose carboplatin modifies the tumor microenvironment to augment CAR T cell efficacy in human prostate cancer models [J].

Porter, L. H. ;

Zhu, J. J. ;

Lister, N. L. ;

Harrison, S. G. ;

Keerthikumar, S. ;

Goode, D. L. ;

Urban, R. Quezada ;

Byrne, D. J. ;

Azad, A. ;

Vela, I. ;

Hofman, M. S. ;

Neeson, P. J. ;

Darcy, P. K. ;

Trapani, J. A. ;

Taylor, R. A. ;

Risbridger, G. P. .

NATURE COMMUNICATIONS, 2023, 14 (01)

[36] Biweekly gemcitabine and low-dose cisplatin in the treatment of locally advanced or metastatic pancreatic cancer patients: a single institute experience [J].

Jordan Lundberg ;

Joshua Reardon ;

Marlo Blazer ;

Gary Phillips ;

Tanios Bekaii-Saab .

Medical Oncology, 2016, 33

[37] Combination therapy with expanded natural killer cells and atezolizumab exerts potent antitumor immunity in small cell lung cancer [J].

Vo, Manh-Cuong ;

Nguyen, Van-Tan ;

Tran, Van-Dinh-Huan ;

Oh, Hyung-Joo ;

Jung, Sung-Hoon ;

Bae, Woo Kyun ;

Lee, Je-Jung ;

Oh, In-Jae .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2025, 74 (04)

[38] Low-dose gemcitabine induces major histocompatibility complex class I-related chain A/B expression and enhances an antitumor innate immune response in pancreatic cancer [J].

Tomoharu Miyashita ;

Kenji Miki ;

Takashi Kamigaki ;

Isamu Makino ;

Hisatoshi Nakagawara ;

Hidehiro Tajima ;

Hiroyuki Takamura ;

Hirohisa Kitagawa ;

Sachio Fushida ;

Ali K. Ahmed ;

Mark D. Duncan ;

John W. Harmon ;

Tetsuo Ohta .

Clinical and Experimental Medicine, 2017, 17 :19-31

[39] Phase II Multicenter trial with carboplatin and gemcitabine induction chemotherapy followed by radiotherapy concomitantly with low-dose paclitaxel and gemcitabine for stage IIIA and IIIB non-small cell lung cancer [J].

Hirsh, Vera ;

Soulieres, Denis ;

Duclos, Marie ;

Faria, Sergio ;

Del Vecchio, Pierre ;

Ofiara, Linda ;

Ayoub, Jean-Pierre ;

Charpentier, Danielle ;

Gruber, James ;

Portelance, Lorraine ;

Souhami, Luis .

JOURNAL OF THORACIC ONCOLOGY, 2007, 2 (10) :927-932

[40] CD137 Stimulation Enhances Cetuximab-Induced Natural Killer: Dendritic Cell Priming of Antitumor T-Cell Immunity in Patients with Head and Neck Cancer [J].

Srivastava, Raghvendra M. ;

Trivedi, Sumita ;

Concha-Benavente, Fernando ;

Gibson, Sandra P. ;

Reeder, Carly ;

Ferrone, Soldano ;

Ferris, Robert L. .

CLINICAL CANCER RESEARCH, 2017, 23 (03) :707-716

← 1 2 3 4 5 →