慢性淋巴细胞白血病中的单核/巨噬细胞研究进展
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摘要
慢性淋巴细胞白血病(chronic lymphocytic leukemia, CLL)作为一种疾病,其进展差异性较大,其中三分之二的患者发展缓慢,另三分之一患者疾病进展较快。常规治疗效果欠佳、常出现药物耐药。近年来研究发现,肿瘤微环境在CLL疾病进展中起到重要作用,单核/巨噬细胞(monocyte/macrophage)作为肿瘤微环境的组成部分,可以通过细胞间相互作用、分泌细胞因子、抑制机体抗肿瘤免疫反应等在CLL中发挥着促肿瘤细胞生长、促耐药等作用。因此,研究单核/巨噬细胞与CLL的关系,可为靶向治疗CLL提供理论依据。本文就单核/巨噬细胞在CLL疾病发展中的作用及相关治疗研究进展作一综述。
Chronic lymphocytic leukemia(CLL)is a malignant hematologic disease with heterogeneous clinical course, about two thirds of patients exhibit a long survival, but the remaining third of patients show aggressiveness of disease or poor response to conventional treatment even drug resistance. Studies suggested that tumor microenvironment possesses a critical effect in CLL disease progression in recent years. Monocyte/macrophage, as an important componens of tumor microenvironment, play a promotive role in the growth and drug reistance of tumor cells by direct cell-to-cell contact, secreting cytokines and suppressing antitumor responses. Therefore, exploring the monocyte/macrophage in CLL can provide theoretic basis for target treatment of CLL. In this review, the function of monocyte/macrophage and recent advances in therapy of CLL are discussed.
Chronic lymphocytic leukemia(CLL)is a malignant hematologic disease with heterogeneous clinical course, about two thirds of patients exhibit a long survival, but the remaining third of patients show aggressiveness of disease or poor response to conventional treatment even drug resistance. Studies suggested that tumor microenvironment possesses a critical effect in CLL disease progression in recent years. Monocyte/macrophage, as an important componens of tumor microenvironment, play a promotive role in the growth and drug reistance of tumor cells by direct cell-to-cell contact, secreting cytokines and suppressing antitumor responses. Therefore, exploring the monocyte/macrophage in CLL can provide theoretic basis for target treatment of CLL. In this review, the function of monocyte/macrophage and recent advances in therapy of CLL are discussed.
引文
1 Rai KR,Jain P.Chronic lymphocytic leukemia(CLL)-Then and now.Am J Hematol,2016;91(3):330-340.
2 Hallek M.Chronic lymphocytic leukemia:2017 update on diagnosis,risk stratification,and treatment.Am J Hematol,2017;92(9):946-965.
3 Medyouf H.The microenvironment in human myeloid malignancies:emerging concepts and therapeutic implications.Blood,2017;129(12):1617-1626.
4 Jenkins SJ,Hume DA.Homeostasis in the mononuclear phagocyte system.Trends Immunol,2014;35(8):358-367.
5方萍,徐可,陈彬,等.巡逻单核细胞在肿瘤中的研究进展.国际肿瘤学杂志,2017;44(5):366-368.
6 Cassetta L,Pollard JW.Cancer immunosurveillance:role of patrolling monocytes.Cell Res,2016;26(1):3-4.
7 Murray PJ.Immune regulation by monocytes.Semin Immunol,2017;DOI:10.1016/j.smim.2017.12.005.
8陆二梅,李益星,白杨,等.巨噬细胞极化的研究进展.现代生物医学进展,2016;32):6397-6400.
9 Chen YCE,Mapp S,Blumenthal A,et al.The duality of macrophage function in chronic lymphocytic leukaemia.Biochim Biophys Acta,2017;1868(1):176-182.
10 Lee HW,Choi HJ,Ha SJ,et al.Recruitment of monocytes/macrophages in different tumor microenvironments.Biochim Biophys Acta,2013;1835(2):170-179.
11 Lahmar Q,Keirsse J,Laoui D,et al.Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment.Biochim Biophys Acta,2016;1865(1):23-34.
12 Blunt MD,Carter MJ,Larrayoz M,et al.The PI3K/mTOR inhibitor PF-04691502 induces apoptosis and inhibits microenvironmental signaling in CLL and the Emicro-TCL1 mouse model.Blood,2015;125(26):4032-4041.
13 Boissard F,Tosolini M,Ligat L,et al.Nurse-like cells promote CLLsurvival through LFA-3/CD2 interactions.Oncotarget,2017;8(32):52225-52236.
14梁峰,赵杨祉,苏龙,等.巨噬细胞对白血病细胞保护作用的研究进展.中国免疫学杂志,2017;33(6):959-961.
15 Boissard F,Fournie JJ,Laurent C,et al.Nurse like cells:chronic lymphocytic leukemia associated macrophages.Leuk Lymphoma,2015;56(5):1570-1572.
16 Ten Hacken E,Burger JA.Microenvironment interactions and B-cell receptor signaling in Chronic Lymphocytic Leukemia:Implications for disease pathogenesis and treatment.Biochim Biophys Acta,2016;1863(3):401-413.
17 De Henau O,Rausch M,Winkler D,et al.Overcoming resistance to checkpoint blockade therapy by targeting PI3Kgamma in myeloid cells.Nature,2016;539(7629):443-447.
18 Hanna BS,Ozturk S,Seiffert M.Beyond bystanders:Myeloid cells in chronic lymphocytic leukemia.Mol Immunol,2017;DOI:10.1016/j.molimm.2017.11.014.
19 Yoshimura T.The chemokine MCP-1(CCL2)in the host interaction with cancer:a foe or ally?Cell Mol Immunol,2018;DOI:10.1038/cmi.2017.135.
20 Galletti G,Scielzo C,Barbaglio F,et al.Targeting macrophages sensitizes chronic lymphocytic leukemia to apoptosis and inhibits disease progression.Cell Rep,2016;14(7):1748-1760.
21 Hanna BS,McClanahan F,Yazdanparast H,et al.Depletion of CLL-associated patrolling monocytes and macrophages controls disease development and repairs immune dysfunction in vivo.Leukemia,2016;30(3):570-579.
22 Mazumdar R,Evans P,Culpin R,et al.The automated monocyte count is independently predictive of overall survival from diagnosis in chronic lymphocytic leukaemia and of survival following first-line chemotherapy.Leuk Res,2013;37(6):614-618.
23 Herishanu Y,Kay S,Sarid N,et al.Absolute monocyte count trichotomizes chronic lymphocytic leukemia into high risk patients with immune dysregulation,disease progression and poor survival.Leuk Res,2013;37(10):1222-1228.
24 Friedman DR,Sibley AB,Owzar K,et al.Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes:a multi-institutional study.Am J Hematol,2016;91(7):687-691.
25 Itchaki G,Brown JR.Experience with ibrutinib for first-line use in patients with chronic lymphocytic leukemia.Ther Adv Hematol,2018;9(1):3-19.
26 Maharaj K,Sahakian E,Pinilla-Ibarz J.Emerging role of BCRsignaling inhibitors in immunomodulation of chronic lymphocytic leukemia.Blood Adv,2017;1(21):1867-1875.
27 Niemann CU,Herman SE,Maric I,et al.Disruption of in vivo Chronic Lymphocytic Leukemia Tumor-Microenvironment Interactions by Ibrutinib-Findings from an Investigator-Initiated Phase II Study.Clin Cancer Res,2016;22(7):1572-1582.
28 Van Attekum MH,Eldering E,Kater AP.Chronic lymphocytic leukemia cells are active participants in microenvironmental crosstalk.Haematologica,2017;102(9):1469-1476.
29 Shaim H,Estrov Z,Harris D,et al.The CXCR4-STAT3-IL-10pathway controls the immunoregulatory function of chronic lymphocytic leukemia and is modulated by lenalidomide.Front Immunol,2017;8(1)70-73).
30 Choi MY,Kashyap MK,Kumar D.The chronic lymphocytic leukemia microenvironment:Beyond the B-cell receptor.Best Pract Res Clin Haematol,2016;29(1):40-53.
31 Shanafelt TD,Ramsay AG,Zent CS,et al.Long-term repair of T-cell synapse activity in a phase II trial of chemoimmunotherapy followed by lenalidomide consolidation in previously untreated chronic lymphocytic leukemia(CLL).Blood,2013;121(20):4137-4141.
32 Strati P,Keating MJ,Burger JA,et al.Consolidation treatment with lenalidomide following front-line or salvage chemoimmunotherapy in chronic lymphocytic leukemia.Haematologica,2017;102(12):e494-e496.
33 Polk A,Lu Y,Wang T,et al.Colony-stimulating factor-1 receptor is required for nurse-like cell survival in chronic lymphocytic leukemia.Clin Cancer Res,2016;22(24):6118-6128.
34 Gautam S,Fatehchand K,Elavazhagan S,et al.Reprogramming Nurse-like Cells with Interferon gamma to Interrupt Chronic Lymphocytic Leukemia Cell Survival.J Biol Chem,2016;291(27):14356-14362.
35 Kaneda MM,Messer KS,Ralainirina N,et al.PI3Kgamma is a molecular switch that controls immune suppression.Nature,2016;539(7629):437-442.
36 Kaneda MM,Cappello P,Nguyen AV,et al.Macrophage PI3Kgamma drives pancreatic ductal adenocarcinoma progression.Cancer Discov,2016;6(8):870-885.
37 Van Dort ME,Galban S,Nino CA,et al.Structure-guided design and initial studies of a bifunctional MEK/PI3K inhibitor(ST-168).ACS Med Chem Lett,2017;8(8):808-813.
2 Hallek M.Chronic lymphocytic leukemia:2017 update on diagnosis,risk stratification,and treatment.Am J Hematol,2017;92(9):946-965.
3 Medyouf H.The microenvironment in human myeloid malignancies:emerging concepts and therapeutic implications.Blood,2017;129(12):1617-1626.
4 Jenkins SJ,Hume DA.Homeostasis in the mononuclear phagocyte system.Trends Immunol,2014;35(8):358-367.
5方萍,徐可,陈彬,等.巡逻单核细胞在肿瘤中的研究进展.国际肿瘤学杂志,2017;44(5):366-368.
6 Cassetta L,Pollard JW.Cancer immunosurveillance:role of patrolling monocytes.Cell Res,2016;26(1):3-4.
7 Murray PJ.Immune regulation by monocytes.Semin Immunol,2017;DOI:10.1016/j.smim.2017.12.005.
8陆二梅,李益星,白杨,等.巨噬细胞极化的研究进展.现代生物医学进展,2016;32):6397-6400.
9 Chen YCE,Mapp S,Blumenthal A,et al.The duality of macrophage function in chronic lymphocytic leukaemia.Biochim Biophys Acta,2017;1868(1):176-182.
10 Lee HW,Choi HJ,Ha SJ,et al.Recruitment of monocytes/macrophages in different tumor microenvironments.Biochim Biophys Acta,2013;1835(2):170-179.
11 Lahmar Q,Keirsse J,Laoui D,et al.Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment.Biochim Biophys Acta,2016;1865(1):23-34.
12 Blunt MD,Carter MJ,Larrayoz M,et al.The PI3K/mTOR inhibitor PF-04691502 induces apoptosis and inhibits microenvironmental signaling in CLL and the Emicro-TCL1 mouse model.Blood,2015;125(26):4032-4041.
13 Boissard F,Tosolini M,Ligat L,et al.Nurse-like cells promote CLLsurvival through LFA-3/CD2 interactions.Oncotarget,2017;8(32):52225-52236.
14梁峰,赵杨祉,苏龙,等.巨噬细胞对白血病细胞保护作用的研究进展.中国免疫学杂志,2017;33(6):959-961.
15 Boissard F,Fournie JJ,Laurent C,et al.Nurse like cells:chronic lymphocytic leukemia associated macrophages.Leuk Lymphoma,2015;56(5):1570-1572.
16 Ten Hacken E,Burger JA.Microenvironment interactions and B-cell receptor signaling in Chronic Lymphocytic Leukemia:Implications for disease pathogenesis and treatment.Biochim Biophys Acta,2016;1863(3):401-413.
17 De Henau O,Rausch M,Winkler D,et al.Overcoming resistance to checkpoint blockade therapy by targeting PI3Kgamma in myeloid cells.Nature,2016;539(7629):443-447.
18 Hanna BS,Ozturk S,Seiffert M.Beyond bystanders:Myeloid cells in chronic lymphocytic leukemia.Mol Immunol,2017;DOI:10.1016/j.molimm.2017.11.014.
19 Yoshimura T.The chemokine MCP-1(CCL2)in the host interaction with cancer:a foe or ally?Cell Mol Immunol,2018;DOI:10.1038/cmi.2017.135.
20 Galletti G,Scielzo C,Barbaglio F,et al.Targeting macrophages sensitizes chronic lymphocytic leukemia to apoptosis and inhibits disease progression.Cell Rep,2016;14(7):1748-1760.
21 Hanna BS,McClanahan F,Yazdanparast H,et al.Depletion of CLL-associated patrolling monocytes and macrophages controls disease development and repairs immune dysfunction in vivo.Leukemia,2016;30(3):570-579.
22 Mazumdar R,Evans P,Culpin R,et al.The automated monocyte count is independently predictive of overall survival from diagnosis in chronic lymphocytic leukaemia and of survival following first-line chemotherapy.Leuk Res,2013;37(6):614-618.
23 Herishanu Y,Kay S,Sarid N,et al.Absolute monocyte count trichotomizes chronic lymphocytic leukemia into high risk patients with immune dysregulation,disease progression and poor survival.Leuk Res,2013;37(10):1222-1228.
24 Friedman DR,Sibley AB,Owzar K,et al.Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes:a multi-institutional study.Am J Hematol,2016;91(7):687-691.
25 Itchaki G,Brown JR.Experience with ibrutinib for first-line use in patients with chronic lymphocytic leukemia.Ther Adv Hematol,2018;9(1):3-19.
26 Maharaj K,Sahakian E,Pinilla-Ibarz J.Emerging role of BCRsignaling inhibitors in immunomodulation of chronic lymphocytic leukemia.Blood Adv,2017;1(21):1867-1875.
27 Niemann CU,Herman SE,Maric I,et al.Disruption of in vivo Chronic Lymphocytic Leukemia Tumor-Microenvironment Interactions by Ibrutinib-Findings from an Investigator-Initiated Phase II Study.Clin Cancer Res,2016;22(7):1572-1582.
28 Van Attekum MH,Eldering E,Kater AP.Chronic lymphocytic leukemia cells are active participants in microenvironmental crosstalk.Haematologica,2017;102(9):1469-1476.
29 Shaim H,Estrov Z,Harris D,et al.The CXCR4-STAT3-IL-10pathway controls the immunoregulatory function of chronic lymphocytic leukemia and is modulated by lenalidomide.Front Immunol,2017;8(1)70-73).
30 Choi MY,Kashyap MK,Kumar D.The chronic lymphocytic leukemia microenvironment:Beyond the B-cell receptor.Best Pract Res Clin Haematol,2016;29(1):40-53.
31 Shanafelt TD,Ramsay AG,Zent CS,et al.Long-term repair of T-cell synapse activity in a phase II trial of chemoimmunotherapy followed by lenalidomide consolidation in previously untreated chronic lymphocytic leukemia(CLL).Blood,2013;121(20):4137-4141.
32 Strati P,Keating MJ,Burger JA,et al.Consolidation treatment with lenalidomide following front-line or salvage chemoimmunotherapy in chronic lymphocytic leukemia.Haematologica,2017;102(12):e494-e496.
33 Polk A,Lu Y,Wang T,et al.Colony-stimulating factor-1 receptor is required for nurse-like cell survival in chronic lymphocytic leukemia.Clin Cancer Res,2016;22(24):6118-6128.
34 Gautam S,Fatehchand K,Elavazhagan S,et al.Reprogramming Nurse-like Cells with Interferon gamma to Interrupt Chronic Lymphocytic Leukemia Cell Survival.J Biol Chem,2016;291(27):14356-14362.
35 Kaneda MM,Messer KS,Ralainirina N,et al.PI3Kgamma is a molecular switch that controls immune suppression.Nature,2016;539(7629):437-442.
36 Kaneda MM,Cappello P,Nguyen AV,et al.Macrophage PI3Kgamma drives pancreatic ductal adenocarcinoma progression.Cancer Discov,2016;6(8):870-885.
37 Van Dort ME,Galban S,Nino CA,et al.Structure-guided design and initial studies of a bifunctional MEK/PI3K inhibitor(ST-168).ACS Med Chem Lett,2017;8(8):808-813.