| Non-Hodgkin's lymphoma mainly includes T and B/NK cell lymphomas and its clinical features are different,the biological characteristics and clinical manifestations are mainly determined by the gene mutation factors related to tumor cells,at present,many researchers pointed out that the tumor microenvironment was closely related to the development and prognosis of lymphoma.Tumor cells and immune cells,such as lymphocytes,dendritic cells,natural killer cells,macrophages are rich in tumor microenvironment.The results showed that the degree of macrophages infiltration was negatively correlated with the survival time of lymphoma patients.The overall survival rate of the patients with high levels of macrophages(>50/hpf)was 22.2%,while with lower amount of macrophages(<50/hpf)was about 52.8%.The macrophages which promote the growth of lymphoma cells are lymphoma-associated macrophages.LAM secretes CCL17,CCL22,CCL24,VEGF and other cytokines,which promote tumor growth and metastasis through the indirect effect of cytokines and tumor cells,the direct effect of LAM and tumor cells,Mononuclear cells in the peripheral blood of lymphoma patients have the potential to transform into LAM,which can promote the growth of tumor cells.Mononuclear cells in the peripheral blood of lymphoma patients have the potential to transform into LAM,promoting the growth of tumor cells.Whether LAM in bone marrow can also promote cancer growth.Cheng et al found that HDAC11 containing conserved regions of deacetylase,by combining the promoter region of IL-10 gene regulating expression and transcription of IL-10 in APC,decrease macrophage antigen presentation function,make T-cells inactivation and tumor cells evading of immune surveillance.HDAC11 was high in patients by detecting the gene in whole blood of myeloproliferative neoplasms.HDAC11 was found to be related to poor prognosis in lymphocytic leukemia.Whether the growth of tumor cells in NHL is related to HDAC11? What is the relationship between the change in HDAC11 and lymphoma-associated macrophages? With the progress of disease,how will HDAC11 change in M2?In this study,by detecting the amount of M2 and secretion of CCL22 in BM of NHL patients in different stages,we know the amount and clinical significance of LAM,by detecting the HDAC11 in M2,we explore its role of pathogenesis.Part 1 Expression of LAM and secretion of tumor growth promoting factor in BM of NHL patientsObjective to detect M2(CD14~+CD68~+CD163~+)amount in BM and the ratio of M2 to M1(CD14~+CD64~+CD80~+)and the expression of CCL22 analyzing the correlation between M2 amount and CCL22 m RNA and clinical indicators,we know the amount of LAM and its clinical significance.Methods From July 2015 to May 2016,44 hospitalized patients in the department of hematology,Tianjin Medical University General Hospital were enrolled in the study,17 cases were of initial treatment and with progressive disease,27 cases were effectively treated and with stable disease.According to the Ann Arbor staging system,37 cases were in stage I ~III,7 cases were in stage IV(all with bone marrow infiltration).9 cases were with B symptoms.30 cases IPI score 0~1,14 cases IPI score?2.18 healthy controls were enrolled.M2 amount in bone marrow and the ratio of M2 to M1 were analyzed using flow cytometry(FCM).CCL22 m RNA expression was analyzed using real-time quantitative PCR(RT-PCR).Results1.The M2 amount in the initial treatment and PD group [(15.25±1.97)%] was higher than in the effectively treated and SD group [(8.11±1.22)%,P=0.04],and in the NC group [(4.53±0.83)%,P=0.0001].The M2/M1 ratio in the initial treatment and PD group [(1.04±0.12)%] was higher than in the effectively treated and SD group[(0.61±0.06)%,P=0.001],and in the NC group [(0.60±0.07)%,P=0.003].2.The M2 amount in T-cell NHL patients [(14.33±1.64)%] was higher than in in B-cell NHL patients [(10.32±1.32)%,P=0.25]3.The M2 amount in stage IV patients [(16.09±1.57)%] was higher than in the stage I~III patients [(9.88±1.31)%,P=0.04].4.The M2 amount in patients with B symptoms [(15.43±1.52)%] was higher than without B symptoms [(9.69±1.37)%,P=0.04].5.The M2 amount in the IPI score ?2 group [(14.58±2.34)%] was higher than in the IPI score 0~1 group [(9.13±1.24)%,P=0.03].6.Patient A(follicular lymphoma IIIA)before chemotherapy M2 amount was.25.93%,after 2 cycles RCHOP treatment,the M2 amount were 7.72% and 0.78%,respectively,decreasing significantly;patients B(diffuse large B cell lymphoma IIIB)before chemotherapy M2 amount was 23.08%.after 2 cycles RCHOP treatment,M2 amount were 4.87% and 1.54%,respectively;patients C(diffuse large B cell lymphoma IIIA)After 6 cycles of RCHOP and 2 cycles of R treatment,the amount of M2 in the stage of CR was 2.57% and 2.13%,the M2 content was 17.78% when the disease progressed.7.The CCL22 m RNA concentration in the initial treatment and PD group[(7.03±1.45)%] was higher than in the effectively treated and SD group[(3.59±0.70)%,P=0.02] and in the NC group [(2.12±0.76)%,P=0.005],there was no statistical difference between the last two groups.8.There were positive correlations between the M2 concentration and the CCL22 m RNA expression level,the LDH and the ?2-MG level(r=0.49,r=0.44,r=0.33;P=0.001,P=0.02,P=0.04).Conclusions the amount of LAM in BM of NHL was associated with the disease efficacy and general body state,not associated with tumor types.With the improvement of disease,LAM and and CCL22 decreased.LAM can represent the tumor load.Part 2 Expression of HDAC11 protein in M2 of NHL patientsObjective By detecting the expression of HDAC11 protein in M2 of NHL patients,exploring the relationship between LAM and tumor growth.Mehtods From July 2015 to May 2016,44 hospitalized patients in the department of hematology,Tianjin Medical University General Hospital were enrolled in the study,17 cases were of initial treatment and with PD,27 cases were effectively treated and with SD,18 healthy controls were enrolled.Cytokines stimulated mononuclear cells of peripheral blood to M2.The expression level of HDAC11 in M2 was detected by Western blot.Results the expression of HDAC11 protein in NHL patients was higher than that in control group,and the expression of HDAC11 in M2 increased with the progression of disease.Conclusions HDAC11 was also one of the internal factors of contributing to the growth of tumor cells in NHL patients.With the progress of the disease,they increased,it is speculated that HDAC11,by reducing the capability of antigen presentation of M1 and enhancing the capability of secreting factors of M2,which can cause immune tolerance,inhibit cell apoptosis. |
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