1. [1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69: 7-34. [DOI:10.3322/caac.21551] [PMID]

2. [2] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424. [DOI:10.3322/caac.21492] [PMID]

3. [3] Miranda-Filho A, Piñeros M, Ferlay J, Soerjomataram I, Monnereau A, Bray F. Epidemiological patterns of leukaemia in 184 countries: a population-based study. Lancet Haematol 2018; 5: e14-e24. [DOI:10.1016/S2352-3026(17)30232-6]

4. [4] Hallek M, Shanafelt TD, Eichhorst B. Chronic lymphocytic leukaemia. The Lancet 2018; 391: 1524-1537. [DOI:10.1016/S0140-6736(18)30422-7]

5. [5] Sindhar S, Kallogjeri D, Wildes TS, Avidan MS, Piccirillo JF. Association of preoperative functional performance with outcomes after surgical treatment of head and neck cancer: a clinical severity staging system. JAMA Otolaryngol Head Neck Surg 2019; 145: 1128-1136. [DOI:10.1001/jamaoto.2019.1035] [PMID] [PMCID]

6. [6] Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood J Am Soc Hematol 2008; 111: 5446-5456. [DOI:10.1182/blood-2007-06-093906] [PMID] [PMCID]

7. [7] Moshfeghi K, Mosayebi G. Therapeutic effects of fludarabine-cyclophosphamide combined therapy in Iranian patients with B-cell chronic lymphocytic leukemia. Koomesh 2015; 16. (Persian).

8. [8] Palma M, Kokhaei P, Lundin J, Choudhury A, Mellstedt H, Österborg A. The biology and treatment of chronic lymphocytic leukemia. Ann Oncol 2006; 17: x144-x154. [DOI:10.1093/annonc/mdl252] [PMID]

9. [9] Kumar R, Godavarthy PS, Krause DS. The bone marrow microenvironment in health and disease at a glance. J Cell Sci 2018; 131: jcs201707. [DOI:10.1242/jcs.201707] [PMID]

10. [10] Pradier A, Passweg J, Villard J, Kindler V. Human bone marrow stromal cells and skin fibroblasts inhibit natural killer cell proliferation and cytotoxic activity. Cell Transplant 2011; 20: 681-691. [DOI:10.3727/096368910X536545] [PMID]

11. [11] Moretta L, Montaldo E, Vacca P, Del Zotto G, Moretta F, Merli P, et al. Human natural killer cells: origin, receptors, function, and clinical applications. Int Arch Allergy Immunol 2014; 164: 253-264. [DOI:10.1159/000365632] [PMID]

12. [12] Nückel H, Switala M, Sellmann L, Horn P, Dürig J, Dührsen U, et al. The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia. Leukemia 2010; 24: 1152. [DOI:10.1038/leu.2010.74] [PMID]

13. [13] Antosz H, Wojciechowska K, Sajewicz J, Choroszyńska D, Marzec-Kotarska B, Osiak M, et al. IL-6, IL-10, c-Jun and STAT3 expression in B-CLL. Blood Cells Mol Dis 2015; 54: 258-265. [DOI:10.1016/j.bcmd.2014.11.006] [PMID]

14. [14] Yan XJ, Dozmorov I, Li W, Yancopoulos S, Sison C, Centola M, et al. Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia. Blood 2011; 118: 5201-5210. [DOI:10.1182/blood-2011-03-342436] [PMID] [PMCID]

15. [15] Katrinakis G, Kyriakou D, Papadaki H, Kalokyri I, Markidou F, Eliopoulos GD. Defective natural killer cell activity in B-cell chronic lymphocytic leukaemia is associated with impaired release of natural killer cytotoxic factor (s) but not of tumour necrosis factor-α. Acta Haematol 1996; 96: 16-23. [DOI:10.1159/000203709] [PMID]

16. [16] Parry HM, Stevens T, Oldreive C, Zadran B, McSkeane T, Rudzki Z, et al. NK cell function is markedly impaired in patients with chronic lymphocytic leukaemia but is preserved in patients with small lymphocytic lymphoma. Oncotarget 2016; 7: 68513. [DOI:10.18632/oncotarget.12097] [PMID] [PMCID]

17. [17] Nagarsheth N, Wicha MS, Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol 2017; 17: 559. [DOI:10.1038/nri.2017.49] [PMID] [PMCID]

18. [18] Guillerey C, Huntington ND, Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol 2016; 17: 1025. [DOI:10.1038/ni.3518] [PMID]

19. [19] Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld RA. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One 2009; 4: e7965. [DOI:10.1371/journal.pone.0007965] [PMID] [PMCID]

20. [20] Huber M, Steinwald V, Guralnik A, Brüstle A, Kleemann P, Rosenplänter C, et al. IL-27 inhibits the development of regulatory T cells via STAT3. Int Immunol 2007; 20: 223-234. [DOI:10.1093/intimm/dxm139] [PMID]

21. [21] Matsui M, Kishida T, Nakano H, Yoshimoto K, Shin-Ya M, Shimada T, et al. Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity. Cancer Res 2009; 69: 2523-2530. [DOI:10.1158/0008-5472.CAN-08-2793] [PMID]

22. [22] Whiteside TL. Isolation of human NK cells and generation of LAK activity. Curr Protoc Immunol 1996; 17: 1-7, 11.

23. [23] Lee HR, Son CH, Koh EK, Bae JH, Kang CD, Yang K, Park YS. Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody. Sci Rep 2017; 7: 1-13. [DOI:10.1038/s41598-017-09259-1] [PMID] [PMCID]

24. [24] Shi C, Tjwa E, Biesta P, Boonstra A, Xie Q, Janssen H, Woltman A. Hepatitis B virus suppresses the functional interaction between natural killer cells and plasmacytoid dendritic cells. J Viral Hepat 2012; 19: e26-e33. [DOI:10.1111/j.1365-2893.2011.01496.x] [PMID]

25. [25] Ghojogh M, Kor Y, Rafiemanesh H. Leukemia in Iran: epidemiology and morphology trends. Asian Pac J Cancer Prev 2015; 16: 7759-7763. [DOI:10.7314/APJCP.2015.16.17.7759] [PMID]

26. [26] Forconi F, Moss P. Perturbation of the normal immune system in patients with CLL. Blood 2015; 126: 573-581. [DOI:10.1182/blood-2015-03-567388] [PMID]

27. [27] Canale S, Cocco C, Frasson C, Seganfreddo E, Di Carlo E, Ognio E, et al. Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model. Leukemia 2011; 25: 1815. [DOI:10.1038/leu.2011.158] [PMID]

28. [28] Keyser J, Schultz J, Ladell K, Elzaouk L, Heinzerling L, Pavlovic J, Moelling K. IP‐10‐encoding plasmid DNA therapy exhibits anti‐tumor and anti‐metastatic efficiency. Exp Dermatol 2004; 13: 380-390. [DOI:10.1111/j.0906-6705.2004.00191.x] [PMID]

29. [29] Dondero A, Casu B, Bellora F, Vacca A, De Luisi A, Frassanito MA, et al. NK cells and multiple myeloma-associated endothelial cells: molecular interactions and influence of IL-27. Oncotarget 2017; 8: 35088. [DOI:10.18632/oncotarget.17070] [PMID] [PMCID]

30. [30] Stabile H, Nisti P, Morrone S, Pagliara D, Bertaina A, Locatelli F, et al. Multifunctional human CD56low CD16low natural killer cells are the prominent subset in bone marrow of both healthy pediatric donors and leukemic patients. Haematologica 2015; 100: 489-498. [DOI:10.3324/haematol.2014.116053] [PMID] [PMCID]

31. [31] Hemati M, Nejad ZR, Shokri MR, Ghahremanfard F, Mohammadkhani MM, Kokhaei P. IL-27 impact on NK cells activity: Implication for a robust anti-tumor response in chronic lymphocytic leukemia. Int Immunopharmacol 2020; 82: 106350. [DOI:10.1016/j.intimp.2020.106350] [PMID]

32. [1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69: 7-34. [DOI:10.3322/caac.21551] [PMID]

33. [2] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424. [DOI:10.3322/caac.21492] [PMID]

34. [3] Miranda-Filho A, Piñeros M, Ferlay J, Soerjomataram I, Monnereau A, Bray F. Epidemiological patterns of leukaemia in 184 countries: a population-based study. Lancet Haematol 2018; 5: e14-e24. [DOI:10.1016/S2352-3026(17)30232-6]

35. [4] Hallek M, Shanafelt TD, Eichhorst B. Chronic lymphocytic leukaemia. The Lancet 2018; 391: 1524-1537. [DOI:10.1016/S0140-6736(18)30422-7]

36. [5] Sindhar S, Kallogjeri D, Wildes TS, Avidan MS, Piccirillo JF. Association of preoperative functional performance with outcomes after surgical treatment of head and neck cancer: a clinical severity staging system. JAMA Otolaryngol Head Neck Surg 2019; 145: 1128-1136. [DOI:10.1001/jamaoto.2019.1035] [PMID] [PMCID]

37. [6] Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood J Am Soc Hematol 2008; 111: 5446-5456. [DOI:10.1182/blood-2007-06-093906] [PMID] [PMCID]

38. [7] Moshfeghi K, Mosayebi G. Therapeutic effects of fludarabine-cyclophosphamide combined therapy in Iranian patients with B-cell chronic lymphocytic leukemia. Koomesh 2015; 16. (Persian).

39. [8] Palma M, Kokhaei P, Lundin J, Choudhury A, Mellstedt H, Österborg A. The biology and treatment of chronic lymphocytic leukemia. Ann Oncol 2006; 17: x144-x154. [DOI:10.1093/annonc/mdl252] [PMID]

40. [9] Kumar R, Godavarthy PS, Krause DS. The bone marrow microenvironment in health and disease at a glance. J Cell Sci 2018; 131: jcs201707. [DOI:10.1242/jcs.201707] [PMID]

41. [10] Pradier A, Passweg J, Villard J, Kindler V. Human bone marrow stromal cells and skin fibroblasts inhibit natural killer cell proliferation and cytotoxic activity. Cell Transplant 2011; 20: 681-691. [DOI:10.3727/096368910X536545] [PMID]

42. [11] Moretta L, Montaldo E, Vacca P, Del Zotto G, Moretta F, Merli P, et al. Human natural killer cells: origin, receptors, function, and clinical applications. Int Arch Allergy Immunol 2014; 164: 253-264. [DOI:10.1159/000365632] [PMID]

43. [12] Nückel H, Switala M, Sellmann L, Horn P, Dürig J, Dührsen U, et al. The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia. Leukemia 2010; 24: 1152. [DOI:10.1038/leu.2010.74] [PMID]

44. [13] Antosz H, Wojciechowska K, Sajewicz J, Choroszyńska D, Marzec-Kotarska B, Osiak M, et al. IL-6, IL-10, c-Jun and STAT3 expression in B-CLL. Blood Cells Mol Dis 2015; 54: 258-265. [DOI:10.1016/j.bcmd.2014.11.006] [PMID]

45. [14] Yan XJ, Dozmorov I, Li W, Yancopoulos S, Sison C, Centola M, et al. Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia. Blood 2011; 118: 5201-5210. [DOI:10.1182/blood-2011-03-342436] [PMID] [PMCID]

46. [15] Katrinakis G, Kyriakou D, Papadaki H, Kalokyri I, Markidou F, Eliopoulos GD. Defective natural killer cell activity in B-cell chronic lymphocytic leukaemia is associated with impaired release of natural killer cytotoxic factor (s) but not of tumour necrosis factor-α. Acta Haematol 1996; 96: 16-23. [DOI:10.1159/000203709] [PMID]

47. [16] Parry HM, Stevens T, Oldreive C, Zadran B, McSkeane T, Rudzki Z, et al. NK cell function is markedly impaired in patients with chronic lymphocytic leukaemia but is preserved in patients with small lymphocytic lymphoma. Oncotarget 2016; 7: 68513. [DOI:10.18632/oncotarget.12097] [PMID] [PMCID]

48. [17] Nagarsheth N, Wicha MS, Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol 2017; 17: 559. [DOI:10.1038/nri.2017.49] [PMID] [PMCID]

49. [18] Guillerey C, Huntington ND, Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol 2016; 17: 1025. [DOI:10.1038/ni.3518] [PMID]

50. [19] Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld RA. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One 2009; 4: e7965. [DOI:10.1371/journal.pone.0007965] [PMID] [PMCID]

51. [20] Huber M, Steinwald V, Guralnik A, Brüstle A, Kleemann P, Rosenplänter C, et al. IL-27 inhibits the development of regulatory T cells via STAT3. Int Immunol 2007; 20: 223-234. [DOI:10.1093/intimm/dxm139] [PMID]

52. [21] Matsui M, Kishida T, Nakano H, Yoshimoto K, Shin-Ya M, Shimada T, et al. Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity. Cancer Res 2009; 69: 2523-2530. [DOI:10.1158/0008-5472.CAN-08-2793] [PMID]

53. [22] Whiteside TL. Isolation of human NK cells and generation of LAK activity. Curr Protoc Immunol 1996; 17: 1-7, 11.

54. [23] Lee HR, Son CH, Koh EK, Bae JH, Kang CD, Yang K, Park YS. Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody. Sci Rep 2017; 7: 1-13. [DOI:10.1038/s41598-017-09259-1] [PMID] [PMCID]

55. [24] Shi C, Tjwa E, Biesta P, Boonstra A, Xie Q, Janssen H, Woltman A. Hepatitis B virus suppresses the functional interaction between natural killer cells and plasmacytoid dendritic cells. J Viral Hepat 2012; 19: e26-e33. [DOI:10.1111/j.1365-2893.2011.01496.x] [PMID]

56. [25] Ghojogh M, Kor Y, Rafiemanesh H. Leukemia in Iran: epidemiology and morphology trends. Asian Pac J Cancer Prev 2015; 16: 7759-7763. [DOI:10.7314/APJCP.2015.16.17.7759] [PMID]

57. [26] Forconi F, Moss P. Perturbation of the normal immune system in patients with CLL. Blood 2015; 126: 573-581. [DOI:10.1182/blood-2015-03-567388] [PMID]

58. [27] Canale S, Cocco C, Frasson C, Seganfreddo E, Di Carlo E, Ognio E, et al. Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model. Leukemia 2011; 25: 1815. [DOI:10.1038/leu.2011.158] [PMID]

59. [28] Keyser J, Schultz J, Ladell K, Elzaouk L, Heinzerling L, Pavlovic J, Moelling K. IP‐10‐encoding plasmid DNA therapy exhibits anti‐tumor and anti‐metastatic efficiency. Exp Dermatol 2004; 13: 380-390. [DOI:10.1111/j.0906-6705.2004.00191.x] [PMID]

60. [29] Dondero A, Casu B, Bellora F, Vacca A, De Luisi A, Frassanito MA, et al. NK cells and multiple myeloma-associated endothelial cells: molecular interactions and influence of IL-27. Oncotarget 2017; 8: 35088. [DOI:10.18632/oncotarget.17070] [PMID] [PMCID]

61. [30] Stabile H, Nisti P, Morrone S, Pagliara D, Bertaina A, Locatelli F, et al. Multifunctional human CD56low CD16low natural killer cells are the prominent subset in bone marrow of both healthy pediatric donors and leukemic patients. Haematologica 2015; 100: 489-498. [DOI:10.3324/haematol.2014.116053] [PMID] [PMCID]

62. [31] Hemati M, Nejad ZR, Shokri MR, Ghahremanfard F, Mohammadkhani MM, Kokhaei P. IL-27 impact on NK cells activity: Implication for a robust anti-tumor response in chronic lymphocytic leukemia. Int Immunopharmacol 2020; 82: 106350. [DOI:10.1016/j.intimp.2020.106350] [PMID]