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Circulating CD16+CD56+ nature killer cells indicate the prognosis of colorectal cancer after initial chemotherapy

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Abstract

As the prognosis of colorectal cancer (CRC) does not always coincide with the pathology and/or surgical findings, a reliable noninvasive prediction tool for the prognosis of CRC is needed. Patients admitted for initial treatment of CRC between January 1, 2015 and December 31, 2015 were retrieved and reviewed. Records of circulating CD16+ CD56+ natural killer (NK) cells were analyzed before and after the initial chemotherapy of FOLFOX plan. Patients were followed up until June 30, 2019. One hundred and twenty-four cases after the FOLFOX chemotherapy were enrolled into this study. There were no significant differences in gender, age, or number of metastasis cases between the survival group and the nonsurvival group (p > 0.05), but significant differences in pre-chemotherapy, post-chemotherapy, and the differences between pre- and post-chemotherapy circulating CD16+ CD56+ NK cells between the survival group and the nonsurvival group (p < 0.01, p < 0.01, and p < 0.05, respectively) were observed. For the prediction of survival and nonsurvival CRC cases, the Areas Under the Curve were 0.626 and 0.759 in the Receiver-Operating Characteristic curves for the pre- and post-chemotherapy circulating CD16+ CD56+NK cells, respectively. Using an optimal cutoff value of 11.8% in post-chemotherapy circulating CD16+CD56+NK cells to differentiate survival and nonsurvival cases, the odds ratio was 0.12 (0.05, 0.27), p < 0.001. The percentages of both pre-chemotherapy and post-chemotherapy circulating CD16+CD56+NK cells were negatively correlated with the prognosis of CRC. The percentage of post-chemotherapy circulating CD16+CD56+NK cells was able to effectively predict the prognosis of CRC cases.

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References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  Google Scholar 

  2. Brody H. Colorectal cancer. Nature. 2015;521(7551):S1.

    Article  CAS  Google Scholar 

  3. Van Cutsem E, Cervantes A, Nordlinger B, Arnold D, ESMO Guidelines Working Group. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):1–9.

    Article  Google Scholar 

  4. Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.

    Article  CAS  Google Scholar 

  5. Peparini N, Beyond T. N and M: the impact of tumor deposits on the staging and treatment of colorectal and gastric carcinoma. Surg Oncol. 2018;27(2):129–37.

    Article  Google Scholar 

  6. Mlecnik B, Marliot F, Bindea G, et al. International validation of the consensus immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018;391(10135):2128–39.

    Article  Google Scholar 

  7. Pawa N, Arulampalam T, Norton JD. Screening for colorectal cancer: established and emerging modalities. Nat Rev Gastroenterol Hepatol. 2011;8(12):711–22.

    Article  CAS  Google Scholar 

  8. Pagès F, Kirilovsky A, Mlecnik B, et al. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer”. J Clin Oncol. 2009;27(35):5944–51.

    Article  Google Scholar 

  9. Pagès F, Berger A, Camus M, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353(25):2654–66.

    Article  Google Scholar 

  10. Rocca YS, Roberti MP, Arriaga JM, et al. Altered phenotype in peripheral blood and tumorassociated NK cells from colorectal cancer patients. Innate Immun. 2013;19(1):76–85.

    Article  CAS  Google Scholar 

  11. Chen ZY, Raghav K, Lieu CH, et al. Cytokine profile and prognostic significance of high neutrophil-lymphocyte ratio in colorectal cancer. Br J Cancer. 2015;112(6):1088–97.

    Article  CAS  Google Scholar 

  12. Biassoni R, Cantoni C, Pende D, et al. Human natural killer cell receptors and co-receptors. Immunol Rev. 2001;181:203–14.

    Article  CAS  Google Scholar 

  13. Benson AB, Venook AP, Al-Hawary MM, et al. NCCN Guidelines Insights Colon Cancer, Version 2.2018. J Natl Compr Canc Netw. 2018;16(4):359–369.

  14. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633–40.

    Article  CAS  Google Scholar 

  15. Dutertre CA, Bonnin-Gelize E, Pulford K, Bourel D, Fridman WH, Teillaud JL. A novel subset of NK cells expressing high levels of inhibitory FcgammaRIIB modulating antibodydependent function. J Leukoc Biol. 2008;84(6):1511–20.

    Article  CAS  Google Scholar 

  16. Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol. 2007;25:297–336.

    Article  CAS  Google Scholar 

  17. Xiong Y, Wang K, Zhou H, Peng L, You W, Fu Z. Profiles of immune infiltration in colorectal cancer and their clinical significant: a gene expression-based study. Cancer Med. 2018;7(9):4496–508.

    Article  CAS  Google Scholar 

  18. Okada K, Sadahiro S, Chan LF, Ogimi T, Miyakita H, Saito G, Tanaka A, Suzuki T. The number of natural killer cells in the largest diameter lymph nodes is associated with the number of retrieved lymph nodes and lymph node size, and is an independent prognostic factor in patients with stage II colon cancer. Oncology. 2018;95(5):288–96.

    Article  CAS  Google Scholar 

  19. Spacek J, Vocka M, Netikova I, Skalova H, Dundr P, Konopasek B, Zavadova E, Lubos P. Immunological examination of peripheral blood in patients with colorectal cancer compared to healthy controls. Immunol Invest. 2018;47(7):643–53.

    Article  CAS  Google Scholar 

  20. Krijgsman D, de Vries NL, Skovbo A, et al. Characterization of circulating T-, NK-, and NKT cell subsets in patients with colorectal cancer: the peripheral blood immune cell profile. Cancer Immunol Immunother. 2019;68(6):1011–24.

    Article  CAS  Google Scholar 

  21. Wang Y, Sun J, Gao W, et al. Preoperative Tim-3 expression on peripheral NK cells is correlated with pathologic TNM staging in colorectal cancer. Mol Med Rep. 2017;15(6):3810–8.

    Article  CAS  Google Scholar 

  22. Brandstadter JD, Yang Y. Natural killer cell responses to viral infection. J Innate Immun. 2011;3(3):274–9.

    Article  CAS  Google Scholar 

  23. Brown MG, Dokun AO, Heusel JW, et al. Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science. 2001;292(5518):934–7.

    Article  CAS  Google Scholar 

  24. Khakoo SI, Carrington M. KIR and disease: a model system or system of models? Immunol Rev. 2006;214:186–201.

    Article  CAS  Google Scholar 

  25. Stewart CA, Laugier-Anfossi F, Vely F, et al. Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. Proc Natl Acad Sci USA. 2005;102(37):13224–9.

    Article  CAS  Google Scholar 

  26. Moretta L, Ciccone E, Mingar MC, Biassoni R, Moretta A. Human natural killer cells: origin, clonality, specificity, and receptors. Adv Immunol. 1994;55:341–80.

    Article  CAS  Google Scholar 

  27. Wagtmann N, Rajagopalan S, Winter CC, Peruzzi M, Long EO. Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer. Immunity. 1995;3(6):801–9.

    Article  CAS  Google Scholar 

  28. Megías J, Yáñez A, Moriano S, O’Connor JE, Gozalbo D, Gil ML. Direct Toll-like receptor-mediated stimulation of hematopoietic stem and progenitor cells occurs in vivo and promotes differentiation toward macrophages. Stem Cells. 2012;30(7):1486–95.

    Article  Google Scholar 

  29. Li K, Li L, Wu X, et al. Loss of SDC1 expression is associated with poor prognosis of colorectal cancer patients in Northern China. Dis Markers. 2019;2019:3768708.

    PubMed  PubMed Central  Google Scholar 

  30. Zhou Z, Ma X, Wang F, Sun L, Zhang G. A matrix metalloproteinase-1 polymorphism, MMP1-1607 (1G > 2G), is associated with increased cancer risk: a meta-analysis including 21,327 patients. Dis Markers. 2018;2018:7565834.

    PubMed  PubMed Central  Google Scholar 

  31. Zhang L, Yang Y, Cheng L, Cheng Y, Zhou HH, Tan ZR. Identification of common genes refers to colorectal carcinogenesis with paired cancer and noncancer samples. Dis Markers. 2018;2018:3452739.

    PubMed  PubMed Central  Google Scholar 

  32. Liu Z, Wu S, Wang L, et al. Prognostic value of MicroRNA-497 in various cancers: a systematic review and meta-analysis. Dis Markers. 2019;2019:2491291.

    PubMed  PubMed Central  Google Scholar 

  33. Chen Y, Wang Z, Zhao G, et al. Performance of a novel blood-based early colorectal cancer screening assay in remaining serum after the blood biochemical test. Dis Markers. 2019;2019:5232780.

    PubMed  PubMed Central  Google Scholar 

  34. Gu J, Xiao Y, Shu D, et al. Metabolomics analysis in serum from patients with colorectal polyp and colorectal cancer by 1H-NMR spectrometry. Dis Markers. 2019;2019:3491852.

    Article  Google Scholar 

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Correspondence to Kejun Nan.

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Cui, F., Qu, D., Sun, R. et al. Circulating CD16+CD56+ nature killer cells indicate the prognosis of colorectal cancer after initial chemotherapy. Med Oncol 36, 84 (2019). https://doi.org/10.1007/s12032-019-1307-8

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  • DOI: https://doi.org/10.1007/s12032-019-1307-8

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