Circulating tumor-associated neutrophils (cTAN) contribute to circulating tumor cell survival by suppressing peripheral leukocyte activation
- 408 Downloads
During malignant progression, primary tumors rebuild leukocyte profile and suppress the host anti-tumor immune response. Tumor-associated neutrophils (TAN) increased in the cancer patients and emerged as an important participant and regulator of immune responses. The aim of this study is to investigate the role of circulating TAN (cTAN) in the metastatic process of advanced malignancy. We tested circulating neutrophils from patients (n = 180) with various types of cancer using flow cytometry analyses. We also used B16F10 cell-implanted C57BL/6 tumor-bearing mice model to simulate the advanced malignancy. Peripheral neutrophils were isolated by ficoll density gradient centrifugation, and in vitro tumor-leukocyte co-culture model was used to test tumor cell survival under leukocyte challenge condition. Here, we showed that neutrophils increased in the peripheral blood under the pathological condition of advanced malignancy both in cancer patients and in tumor-bearing mice. In mouse model, the malignantly increased neutrophils were identified as TAN according to the gene transcriptional analyses. We also showed that cTAN enhance tumor metastasis and cTAN could inhibit the activation of the peripheral leukocytes and rescue tumor cells from leukocyte challenge. In conclusion, our finding suggests that the abundance of cTAN in advanced cancer patients contributes to the circulating tumor cell survival by suppressing peripheral leukocyte activation.
KeywordsNeutrophil Tumor-associated neutrophil Tumor metastasis Tumor cell survival
This work was supported by the grants from National Nature Science Foundation of China (81372288, 81172014) and the Natural Science Foundation of Jilin province (20150101186JC). We also would like to acknowledge the assistance of the Experimental Animal Center of NENU for the animal care, the Clinical Laboratory of the Second People’s Hospital of Jilin for the collection of clinical blood samples, and Yanyan Gao (NENU) for the stable transfected GFP positive B16F10 cell line.
Compliance of ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration andits later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Conflicts of interest
- 9.Kapp A, McKenna KC. Accumulation of immunosuppressive CD11b+ myeloid cells correlates with the failure to prevent tumor growth in the anterior chamber of the Eye1. J Immunol. 2006;3:1599–608.Google Scholar
- 15.Tazawa H, Okada F, Kobayashi T, et al. Infiltration of neutrophils is required for acquisition of metastatic phenotype of benign murine fibrosarcoma cells: implication of inflammation-associated carcinogenesis and tumor progression. Am J Pathol. 2003;163:2221–32.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Oliveira AG, Guabiraba R, Teixeira MM, Menezes G. Tumor-associated neutrophils. Trends Stem Cell Prolif Cancer Res 2013;479–501.Google Scholar
- 30.Katarina R, Jan HN. CD69 is the crucial regulator of intestinal inflammation: a new target molecule for IBD treatment? J Immunol Res. 2015;2015:1–12.Google Scholar