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Granulocytes Acquire Antiapoptosis Activity and Promote Tumor Growth during Tumor ProgressFunding None.
Granulocytes play important roles in cancer, and their apoptotic status is often changed by the influence of tumor environment. However, the changes and the function on granulocyte apoptosis in cancer are unclear. In this study, we used tumor-bearing mouse model and tumor patients to analyzed the apoptosis of granulocytes in different tissues by flow analysis and TUNEL fluorescence staining, and found that the percentage of apoptosis cells in granulocytes was significantly decreased in late-stage tumor-bearing mouse and patients. The in vitro co-culture experiment showed that these antiapoptotic granulocytes could significantly inhibit T cell proliferation, and RNA-seq proved that there was obvious difference on the transcriptome between these cells and control cells, particularly immune-related genes. What is important, adoptive transfer of these antiapoptotic granulocytes promoted tumor progress in mouse model. Conclusively, we found that granulocytes in late-stage tumor could delay the process of apoptosis, inhibit T cell proliferation, and acquire pro-tumor activity, which provides a new therapeutic target for tumor immunity.
* These authors contributed equally to this work.
16 March 2021 (online)
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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- 1 Fridlender ZG, Sun J, Kim S. et al. Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell 2009; 16 (03) 183-194
- 2 Rachidi S, Wallace K, Wrangle JM, Day TA, Alberg AJ, Li Z. Neutrophil-to-lymphocyte ratio and overall survival in all sites of head and neck squamous cell carcinoma. Head Neck 2016; 38 (Suppl. 01) E1068-E1074
- 3 Cartwright JA, Lucas CD, Rossi AG. Inflammation resolution and the induction of granulocyte apoptosis by cyclin-dependent kinase inhibitor drugs. Front Pharmacol 2019; 10: 55
- 4 Fox S, Leitch AE, Duffin R, Haslett C, Rossi AG. Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease. J Innate Immun 2010; 2 (03) 216-227
- 5 Geering B, Simon H-U. Peculiarities of cell death mechanisms in neutrophils. Cell Death Differ 2011; 18 (09) 1457-1469
- 6 Sagiv JY, Michaeli J, Assi S. et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Reports 2015; 10 (04) 562-573
- 7 Maianski NA, Maianski AN, Kuijpers TW, Roos D. Apoptosis of neutrophils. Acta Haematol 2004; 111 (1-2): 56-66
- 8 Schmielau J, Finn OJ. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients. Cancer Res 2001; 61 (12) 4756-4760
- 9 Kanno H, Nishihara H, Wang L. et al. Expression of CD163 prevents apoptosis through the production of granulocyte colony-stimulating factor in meningioma. Neuro-oncol 2013; 15 (07) 853-864
- 10 Rodriguez PC, Ernstoff MS, Hernandez C. et al. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 2009; 69 (04) 1553-1560
- 11 Fridlender ZG, Sun J, Mishalian I. et al. Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils. PLoS One 2012; 7 (02) e31524