Rational targeting of immunosuppressive neutrophils in cancer

doi:10.1016/j.pharmthera.2020.107556

Review

. 2020 Aug:212:107556.

doi: 10.1016/j.pharmthera.2020.107556. Epub 2020 Apr 25.

Rational targeting of immunosuppressive neutrophils in cancer

Yun Zhao¹, Sharif Rahmy², Zhongmin Liu³, Chao Zhang⁴, Xin Lu⁵

Affiliations

¹ Department of Cardiac Surgery, Shanghai East Hospital, Tongji University, Shanghai 200092, China; Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
² Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
³ Department of Cardiac Surgery, Shanghai East Hospital, Tongji University, Shanghai 200092, China.
⁴ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: zhangchao@tongji.edu.cn.
⁵ Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA; Tumor Microenvironment and Metastasis Program, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA. Electronic address: xlu@nd.edu.

PMID: 32343986
DOI: 10.1016/j.pharmthera.2020.107556

Review

Rational targeting of immunosuppressive neutrophils in cancer

Yun Zhao et al. Pharmacol Ther. 2020 Aug.

. 2020 Aug:212:107556.

doi: 10.1016/j.pharmthera.2020.107556. Epub 2020 Apr 25.

Authors

Yun Zhao¹, Sharif Rahmy², Zhongmin Liu³, Chao Zhang⁴, Xin Lu⁵

Affiliations

¹ Department of Cardiac Surgery, Shanghai East Hospital, Tongji University, Shanghai 200092, China; Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
² Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
³ Department of Cardiac Surgery, Shanghai East Hospital, Tongji University, Shanghai 200092, China.
⁴ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: zhangchao@tongji.edu.cn.
⁵ Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA; Tumor Microenvironment and Metastasis Program, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA. Electronic address: xlu@nd.edu.

PMID: 32343986
DOI: 10.1016/j.pharmthera.2020.107556

Abstract

Neutrophils, the most abundant circulating leukocytes in human, play an indispensable role in the innate immune response to microbial infections. However, the contribution of tumor-associated neutrophils (TANs) to cancer progression and tumor immunity has been a matter of debate for decades. A higher neutrophil-to-lymphocyte ratio is associated with adverse overall survival in many solid tumors. Preclinical evidence exists to support both anti-tumor and pro-tumor activities of TANs, and TANs employ diverse mechanisms to influence tumor progression and metastasis. Here, we focus our review on the immunosuppressive mechanism of TANs and highlight how neutrophils can operate to dampen both innate and adaptive immunity to promote tumorigenesis. Here we discuss the intriguing and sometimes controversial connection between TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells (G/PMN-MDSCs). The molecular mechanisms underlying neutrophils' role in immunosuppression provide potential therapeutic targets for cancer treatment, either as monotherapies or as a part of combinatorial regimens. Therefore, we also highlight a number of neutrophil-targeting approaches that may improve the efficacy of current anticancer therapies, especially cancer immunotherapy. Currently interest is surging in the understanding and targeting of immunosuppressive neutrophils, with the goal of developing novel therapeutic strategies in the battle against cancer.

Keywords: Immuno-oncology; Immunosuppression; Immunotherapy; Neutrophil; PMN-MDSC; Tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that there are no conflicts of interest.

Cited by

Complement factor H: a novel innate immune checkpoint in cancer immunotherapy.
Saxena R, Gottlin EB, Campa MJ, Bushey RT, Guo J, Patz EF Jr, He YW. Saxena R, et al. Front Cell Dev Biol. 2024 Feb 8;12:1302490. doi: 10.3389/fcell.2024.1302490. eCollection 2024. Front Cell Dev Biol. 2024. PMID: 38389705 Free PMC article. Review.
T lymphocyte and neutrophil/lymphocyte ratio in patients with radiation-induced oral mucositis after intensity-modulated radiation therapy for head and neck cancer: A retrospective single-center study.
Qi S, Yin L, Jia K, Zhang N, Shi Y, Caihang Q, Jia Z, Quan J. Qi S, et al. Medicine (Baltimore). 2024 May 31;103(22):e38355. doi: 10.1097/MD.0000000000038355. Medicine (Baltimore). 2024. PMID: 39259120 Free PMC article.
Bidirectional crosstalk between therapeutic cancer vaccines and the tumor microenvironment: Beyond tumor antigens.
Zhang SW, Wang H, Ding XH, Xiao YL, Shao ZM, You C, Gu YJ, Jiang YZ. Zhang SW, et al. Fundam Res. 2022 Mar 26;3(6):1005-1024. doi: 10.1016/j.fmre.2022.03.009. eCollection 2023 Nov. Fundam Res. 2022. PMID: 38933006 Free PMC article. Review.
The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer-Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy.
Starska-Kowarska K. Starska-Kowarska K. Cancers (Basel). 2023 Mar 7;15(6):1642. doi: 10.3390/cancers15061642. Cancers (Basel). 2023. PMID: 36980527 Free PMC article. Review.
Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Patients with Mycosis Fungoides.
Di Raimondo C, Lombardo P, Tesei C, Esposito F, Meconi F, Secchi R, Lozzi F, Monopoli A, Narducci MG, Scala E, Angeloni C, De Stefano A, Rahimi S, Bianchi L, Cantonetti M. Di Raimondo C, et al. Diagnostics (Basel). 2023 Jun 5;13(11):1979. doi: 10.3390/diagnostics13111979. Diagnostics (Basel). 2023. PMID: 37296831 Free PMC article.

See all "Cited by" articles

Publication types

Actions
Actions

MeSH terms

Substances

LinkOut - more resources

Full Text Sources
- Elsevier Science

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Rational targeting of immunosuppressive neutrophils in cancer

Affiliations

Rational targeting of immunosuppressive neutrophils in cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Abstract

Conflict of interest statement

Similar articles

Cited by

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources