Prognostic significance of T cell subsets in peripheral blood of B cell non-Hodgkin’s lymphoma patients

The role of tumor-infiltrating T cell subsets in the prognosis of non-Hodgkin's lymphoma (NHL) has previously been reported. In the present study, we investigated the prognostic significance of different T cell subsets in the peripheral blood of NHL patients. Immunophenotyping was performed on the peripheral blood samples of 45 patients with newly diagnosed B cell NHL using flow cytometry. The relationship between T cell subsets of CD4+, CD8+, CD3+CD25+, CD4+CD25+, CD4+CD25(high) [as T regulatory cells (T reg)], and the CD4/CD8 ratio with international prognostic index (IPI) and response to therapy was determined. The percentages of CD3+, CD4+, and CD8+?T cells in the peripheral blood of the patients were 49.1?±?20.3%, 23.6?±?11%, and 31.4?±?14.4%, respectively (CD4/CD8 ratio: 0.92?±?0.6). There were 4.2?±?3.2% T reg cells. A study of the percentage of T cells in relation to IPI score showed a higher proportion of CD3+CD25+, CD4+, and CD4+CD25+ cells in low-risk patients compared with intermediate/high risk groups (p?相似文献   

Pretreatment T Lymphocyte Numbers Are Contributing to the Prognostic Significance of Absolute Lymphocyte Numbers in B-cell Non-Hodgkins Lymphomas

Targeted immuno-chemotherapy resulted in greatly improved survival of B cell lymphoma patients. Several prognostic markers are investigated, amongst them the pretreatment absolute lymphocyte numbers. We investigated lymphocyte subpopulations and correlated this data with prognosis of patients. 88 patients (mean age: 56 years, 18–88, median follow up 32 months) with B cell lymphomas were investigated. There were 51 DLBCL, 16 Follicular NHL, 4 MALT, 7 Marginal Zone NHL, 10 Small lymphocytic cases were investigated. Our data showed that overall survival was statistically significant up to the 0.9 G/l absolute lymphocyte numbers as dividers between the subgroups. The CD19+ B cell numbers, or the CD56+/CD3- NK cell numbers did not represent any significant differences between subgroups. However CD3+, CD4+ and CD8+ T cells were differentiating statistically significant subgroups. Pretreatment CD3+ cell number less than 700/ul and CD8+ cell number less than 200/ul were corresponding with significantly inferior overall survival. These could be verified in the bad prognostic IPI group as well. Our data further support the importance of pretreatment lymphocyte numbers and highlight CD3+ and CD8+ lymphocytes to be the key factors in predicting outcome.     

Immunologic markers in non-Hodgkin's lymphoma

The majority of non-Hodgkin's lymphomas (NHLs) are of B-cell lineage, with less than 20% of cases being of T-cell lineage. The B-cell NHLs phenotypically correspond to normal cells in the mid stages of normal differentiation. More specifically, by their expression of B-cell activation antigens, these tumors are the neoplastic counterparts of normal activated B cells. The follicular lymphomas--including the small cleaved, mixed small and large cell, and large cell types, as well as the small noncleaved cell (Burkitt's) lymphomas--represent malignant expansions of normal germinal center B cells by their expression of pan-B cell antigens, B-cell activation antigens, and CD10 (CALLA). The diffuse lymphomas also correspond to normal activated B cells. The small lymphocytic lymphomas express the low-affinity IL-2 receptor and CD5, both of which are induced on normal B cells following mitogen stimulation. The other diffuse B-cell NHLs similarly express activation antigens and resemble "transformed" B cells. The T-cell NHLs generally correspond to normal activated CD4+ T cells. These tumors--which include most peripheral T-cell lymphomas, cutaneous T-cell lymphomas, and HTLV-I-associated adult T-cell leukemias/lymphomas--express antigens induced on activated T cells, including IL-2 and transferrin receptors (CD25 and CD71, respectively), as well as HLA-DR. The lymphoblastic lymphomas, which are generally of T-cell lineage, phenotypically correspond to stages of intrathymic differentiation, often by their coexpression of CD4 and CD8, as well as expression of CD1. It remains controversial whether the immunophenotype of lymphoblastic lymphoma differs significantly from T-cell acute lymphoblastic leukemia. Since immunologic heterogeneity of NHL was first observed, attempts have been made to employ the data as a prognostic variable. Early studies suggested that lineage derivation or expression of markers of proliferating cells affected outcome in NHL. However, these reports were often retrospective, included various histologies, and did not treat patients uniformly. More recent prospective studies with relatively uniformly treated patients, predominantly involving DLCL, suggest that certain immunologically defined subgroups may have significantly different clinical outcomes. However, additional clinical studies will be necessary before treatment options are based upon immunologic markers.     

Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression.

Rituximab is a chimeric antibody with human gamma-1 and kappa constant regions and murine variable regions. It recognizes the CD20 antigen, a pan B-cell marker. Therapeutic trials in patients with B-cell non-Hodgkin's lymphoma (NHL) have shown significant efficacy with a primary response rate of 50%, and a secondary response rate of 44% after repeat treatments in prior responders. The selection for proliferating tumor cells that no longer express CD20 may compromise repeated treatment. We have identified a patient who developed a transformed NHL that lost CD20 protein expression after two courses of therapy with rituximab. In a pretreatment lymph node biopsy, 83% of B cells (as defined by CD19 and surface immunoglobulin) expressed surface CD20. A biopsy from the recurrent tumor after two courses of rituximab revealed a diffuse large cell NHL where 0% of B cells expressed CD20 with no evidence of bound rituximab. Cytoplasmic staining showed no CD20 protein. Sequencing of immunoglobulin heavy chain cDNA identified identical variable sequences in the initial and recurrent lymphomas, confirming the association between the two tumors. Literature and database review suggests that approximately 98% of diffuse large cell lymphomas express CD20, which suggests that these tumors rarely survive without CD20. This is the first identified case of loss of CD20 expression in a lymphoma that has relapsed after rituximab therapy, although several other cases have since been identified. Considering the significant number of patients treated with anti-CD20 antibodies, this may occur only rarely and is unlikely to preclude recurrent therapy with anti-CD20 antibodies in the majority of patients. However, because many patients have relapsed after anti-CD20 antibody therapy and have not been biopsied to identify clones with down-regulated CD20 antigen, we do not currently know the true frequency of this phenomenon. When possible, patients should undergo evaluation for CD20 expression before repeated courses of anti-CD20 therapy.     

Attenuation of CD8(+) T-cell function by CD4(+)CD25(+) regulatory T cells in B-cell non-Hodgkin's lymphoma

The underlying mechanisms by which tumor cells are resistant to CTL-mediated apoptosis are not clear. Using a human model of B-cell non-Hodgkin's lymphoma (B-cell NHL), we show that intratumoral T(reg) cells inhibit the proliferation and granule production of activated autologous infiltrating CD8(+) T cells. Our results also show that degranulation and subsequent cytotoxic activity of infiltrating CD8(+) T cells exposed to lymphoma B cells is completely attenuated by the presence of intratumoral T(reg) cells. Furthermore, we show that increased numbers of intratumoral T(reg) cells correlates with the number of CD8(+) T cells in biopsy specimens from patients with B-cell NHL, supporting the in vitro findings that intratumoral T(reg) cells inhibit proliferation of infiltrating CD8(+) T cells. Taken together, these data indicate that human lymphoma B cells are sensitive to autologous CTL-mediated cell death but are protected by the inhibitory function of intratumoral T(reg) cells.     

Effect of blood transfusion during radiotherapy on the immune function of patients with cancer of the uterine cervix: role of interleukin-10

: To analyze prospectively the effects of blood transfusion administered during radiotherapy (RT) on the immune function of patients with locally advanced cervical cancer.

: In a total of 15 patients, 7 transfused and 8 untransfused, lymphocyte populations, including CD3+, CD4+, and CD8+ T-cell subsets, B cells (CD19+), and natural killer (NK) cells (CD56+, CD16+, CD3−) were studied before (i.e., time 0), during (i.e., times 1 and 2), and after (i.e., time 3) therapy. Expression of the early (CD25) and late (HLA-DR) activation markers on CD3+ T cells, the intracellular levels of perforin in CD8+ and CD56+ cells, and interferon (IFN)-γ, interleukin (IL)-2, and IL-4 in CD4+ and CD8+ T cells were also measured. NK cell cytotoxicity against the NK-sensitive target K-562 cells and CD8+ T-cell-directed cytotoxicity against OKT3 hybridoma cells were also assessed. Finally, the plasma levels of the immunoregulatory cytokine IL-10 were analyzed by enzyme-linked immunosorbent assay.

: The mean absolute number of all lymphocyte subsets compared with pretreatment levels decreased significantly during RT of both transfused and untransfused patients (p >0.001), with no detectable differences between the two groups in terms of total lymphocytes or relative numbers of CD3+ and CD4+ T cells, CD56+ NK cells, or CD19+ B cells. In contrast, concomitant with an inversion of the CD4/CD8 ratio, a significant increase in the number of CD8+ T cells at time 2 and CD3+ T cells, CD8+ T cells, and NK cells at time 3 was found in the transfused patients compared with the untransfused group. The percentages of CD25+/CD3+ T cells and HLA-DR+/CD3+ T cells increased during RT of the untransfused patients, but CD3+ T cells showed decreased CD25 expression and increased HLA-DR expression in the transfused group. An increase of CD8+ IFN-γ+ T cells with a concomitant decrease in CD8+ IL-2+ T cells was found in the transfused vs. untransfused group, and no differences were noted in the percentage of CD4+ IFN-γ+ T cells and CD4+ IL-2+ T cells. The proportion of perforin-positive CD8+ and CD56+ cells was higher in the transfused group than in the untransfused group. However, CD56+ cells and CD8+ T cells from the transfused patients showed markedly diminished cytotoxic function. Finally, IL-10 was detected only in the plasma of the transfused patients.

: Blood transfusion during primary RT for cervical cancer profoundly alters the magnitude and characteristics of radiation-induced immunosuppression. Elevated serum IL-10 in transfused patients may play a role in the disregulation of lymphocyte function, in particular, the depression of NK- and T-cell cytotoxicity. Investigation of alternatives to blood transfusion during RT that do not diminish host immunity is warranted.     

CD4+CD29+T细胞含量及其免疫检查点水平与非小细胞肺癌患者的化疗效果及远期存活率的关系

目的分析CD4+CD29+T细胞含量及细胞毒性T淋巴细胞相关抗原4(CTLA 4)、程序坏死因子1(PD 1)及程序坏死因子配体1(PD L1)免疫检查点表达水平与非小细胞肺癌患者的化疗效果及远期存活率的关系。方法选取2015年1月至2017年1月沧州市中心医院收治的100例非小细胞肺癌患者;采用流式细胞术检测患者血中CD4+CD29+T、CTLA 4+T、PD 1+T及PD L1+T细胞水平;随访2年,记录患者生存情况,分为存活组79例,死亡组21例;依照RECIST Version 11标准对患者化疗效果进行评估,并按此分为缓解组54例,进展组46例。比较各组的CD4+CD29+T、CTLA 4+T、PD 1+T及PD L1+T细胞水平,分析以上各细胞水平与患者疗效及远期存活率之间的相关关系。结果化疗缓解组CD4+CD29+T、CTLA 4+T及PD 1+T细胞水平均高于进展组［(2274±192)％ vs.(1804±215)％、(2891±124)％ vs.(2013±177)％、(2629±119)％ vs.(1894±164)％］,PD L1+T细胞水平低于进展组［(1722±107)％ vs.(2273±125)％］,差异均有统计学意义(P<005);存活组CD4+CD29+T、CTLA 4+T及PD 1+T细胞水平均高于死亡组［(2211±117)％ vs.(1481±164)％、(2832±124)％ vs.(1190±193)％、(2588±201)％ vs.(1173±206)％］,PD L1+T细胞水平低于死亡组［(1641±272)％ vs.(2481±211)％］,差异均有统计学意义(P<005)。CD4+CD29+T、CTLA 4+T、PD 1+T细胞水平与患者疗效及远期存活率呈正相关(P<005),PD L1+T细胞水平与患者疗效及远期存活率呈负相关(P<005)。结论非小细胞肺癌患者血中CD4+CD29+、CTLA 4+、PD 1+T细胞水平与化疗效果及远期生存呈正相关,PD L1+T细胞水平与其呈负相关关系。     

调节性T细胞在口腔鳞癌患者外周血及癌组织中的表达和意义

目的 探讨CD4+CD25+Foxp3+调节性T细胞（regulatory T cell,Treg）在口腔鳞癌患者外周血及癌组织中的表达和意义。方法 选取初诊的30例口腔鳞癌患者,按临床分期分为A、B两组,A组为Ⅰ、Ⅱ期患者,B组为Ⅲ、Ⅳ期患者,10例健康志愿者为对照组（C组）。分别采集三组受试对象晨起空腹外周血3 ml,采用流式细胞术测定外周血中CD4+CD25+Foxp3+调节性T细胞、CD80、CD86和HLA-DR的表达情况;取试验组及对照组手术标本,利用免疫组织化学法测定Foxp3+调节性T细胞的浸润情况。结果 CD4+CD25+Foxp3+T淋巴细胞占CD4+ T淋巴细胞比例在三组中分别为（2.80±0.90）%(A组)、（5.09±1.72）%（B组）、（0.57±0.15）%（C组） , 组间比较差异具有统计学意义（P=0.000）。A、B组外周血中单个核细胞表面共刺激分子CD80+CD86+、 CD80+HLA-DR+及CD86+HLADR+细胞的表达明显低于C组;CD4+CD25+Foxp3+调节性T细胞所占比例与CD80+CD86+、CD80+HLA-DR+和CD86+HLA-DR+表达率进行直线相关分析,相关系数分别为-0.512、-0.430、-0.461,均有统计学意义。免疫组织化学结果显示,Foxp3在口腔鳞癌组织中主要分布在黏膜固有层肿瘤间质,其中Foxp3+调节性T细胞在高分化和中分化口腔鳞癌中少,在低分化口腔鳞癌中多,两者间差异有统计学意义。结论 检测口腔癌患者外周血和肿瘤组织中CD4+CD25+Foxp3+调节性T胞,有助于对机体抗肿瘤免疫水平、病变进展情况和肿瘤预后进行评估,为临床生物治疗提供佐证。     

Coexistence of Philadelphia-positive chronic granulocytic leukemia and diffuse large B-cell lymphoma at initial diagnosis

We describe the rare coexistence at the time of diagnosis of Philadelphia positive chronic myelogenous leukemia (Ph+ CML) and non-Hodgkin's lymphoma (NHL). At the time of diagnosis, cytogenetic analysis of peripheral blood and bone marrow cells revealed the Ph chromosome translocation in all examined metaphases. The lymph node biopsy showed features of diffuse large B-cell lymphoma (DLBCL). This case may be of interest due to: (1) the rare coexistence of Ph+ CML and NHL at diagnosis, (2) the fact, that in contrary with previously reported cases in patients with antecedent or concurrent diagnosis of CML, where precursor lymphoblastic lymphomas are prevalent, in our patient clinical and laboratory findings revealed a diffuse large B-cell lymphoma, and (3) that the present case is an additional one confirming the poor outcome of patients with simultaneous occurrence of these two clinical entities.     

Expression pattern of hybrid phenotype in adult acute lymphoblastic leukemia.

We examined the expression of hybrid phenotype in 236 adults with acute lymphoblastic leukemia (ALL; 188 B-lineage ALL and 48 T-lineage ALL). In B-lineage ALL, myeloid antigen (mAg) CD15 was concentrated in CD10-CD20- cases (49%); CD13 (42%); and CD33 (43%) in CD10+CD20- cases. This trend had no correlation with the presence of Ph1 or t(4;11) chromosomal abnormality. T-cell antigen CD2, CD4, and CD7 was seen in four, four, and two cases, respectively, and CD4+ and CD7+ cases commonly expressed CD13 and/or CD33 (CD13/CD33). In T-lineage ALL, expression of mAg, CD11b (47%), CD13 (38%), CD15 (28%), and CD33 (51%) was restricted to CD3- cases. B-cell antigen CD19 was found in two cases with CD7 solely as T-cell antigen, and these cases possessed CD13/CD33. CD21 was detected in three cases with CD3. In whole ALL, CD13/CD33 was associated closely with the presence of stem-cell antigen CD34, and in T-lineage ALL, CD13/CD33 had a significant correlation with additional stem-cell features, such as HLA-DR, multidrug resistance 1 (MDR1) and c-kit gene expression. Our results suggest that immature ALL cells frequently express B+M+, T+M+, and occasionally B+T+M+ phenotype; that B+T+M- phenotype is extremely rare; and that mAg expression in B-lineage ALL is complicated as compared to T-lineage ALL.     

The potential palliative role and possible immune modulatory effects of low-dose total body irradiation in relapsed or chemo-resistant non-Hodgkin's lymphoma.

In a group of 35 patients with relapsed and/or chemo-resistant non-Hodgkin's lymphoma (NHL), low-dose total body irradiation (LTBI) (+involved-field radiotherapy to bulky sites) achieved a complete remission rate of 29%, 2-years progression-free survival of 32% and a median progression-free survival of 12 months. The 2-year survival was 42% and the median survival was 17 months. Immuno-staining and flow cytometry of peripheral blood in 14 patients showed that LTBI leads to a significant increase in the percentage of CD4+ cells with a consequent significant increase in the CD4+/CD8+ ratio. High lymphocytic percent and a high percentage of CD4+ cells before LTBI were significantly correlated with longer response duration and overall survival. These data may suggest that the palliative potential of LTBI should be investigated as an alternative to chemotherapy in NHL patients. The pre-treatment percentage of lymphocytes and CD4+ cells may be used as predictors for response to LTBI.     

肺癌患者外周血 T- 淋巴细胞亚群 NK 细胞的基线数值及其与预后的关系*

目的:对比肺癌患者与健康者之间淋巴细胞亚群差异,评估肺癌患者外周血T 淋巴细胞亚群及自然杀伤细胞（NK）之基线值与预后的关系。方法:收集2006年2 月至2013年3 月就诊于天津医科大学肿瘤医院病例资料完整的肺癌患者105 例,其中非小细胞肺癌（NSCLC ）86例、小细胞肺癌（SCLC）19例,另选健康对照35例,对比接受治疗前肺癌患者和健康对照者外周血中的CD3+T 细胞、CD4+T 细胞、CD8+T 细胞及NK细胞所占百分比,并回顾性分析86例NSCLC 患者初治时外周血淋巴细胞亚群与预后的关系。结果:肺癌患者外周血CD3+T 细胞、CD4+T 细胞、NK细胞及CD4/CD 8 比值均明显低于健康对照组（P = 0.011,P = 0.007,P <0.001,P=0.025）,而CD8+T 细胞比例高于健康对照组（P = 0.013）。 当CD8+T ≥ 31.8% 及CD4/CD 8< 1.28时NSCLC 患者可以获得一个更长的OS（中位OS分别为36.2 m vs . 20.0 m ,P = 0.010;30.8 m vs . 20.0 m ,P = 0.035）。 而CD3+T 细胞、CD4+T 细胞及NK细胞百分比对NSCLC 患者预后无显著影响。结论:外周血CD8+T 细胞基线水平较高的NSCLC 患者生存较长,此基线水平可能对NSCLC 患者预后有指示作用。      

Bone marrow involvement by non-Hodgkin's lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group.

Bone marrow specimens from 317 patients with non-Hodgkin's lymphoma (NHL) obtained at initial staging were evaluated for the presence of lymphoma or benign lymphoid aggregates. Thirty-two percent (102 patients) had lymphoma in their bone marrow, and 9% had benign lymphoid aggregates. Bone marrow lymphoma was present in 39% of low-grade, 36% of intermediate-grade, and 18% of high-grade lymphomas. The bone marrow was involved in 25% of patients with diffuse large-cell or immunoblastic NHL (ie, diffuse histiocytic lymphoma of Rappaport). Bone marrow involvement did not affect survival of patients with low-grade NHL, but survival was significantly shorter (P = .03) for patients with intermediate- and high-grade NHL with bone marrow involvement. Bone marrow involvement was equally common in B-cell and T-cell NHL (31% v 32%). However, patients with T-cell NHL and bone marrow involvement had shorter survival than B-cell NHL with marrow involvement (P = .02) or T-cell NHL without marrow involvement (P = .05). A high incidence of morphologic discordance between lymph node and bone marrow was observed (ie, 40%), always with a more aggressive subtype in the lymph node than in the bone marrow. Presence of large-cell lymphoma in the bone marrow predicted for short survival. Survival for patients with small-cell lymphoma in their bone marrow did not differ significantly from patients with negative bone marrows. We conclude that bone marrow involvement in large-cell NHL, especially in those of T-cell origin, portends a poor prognosis. However, the subgroup of patients with an aggressive histologic subtype of NHL in a lymph node biopsy and small-cell NHL in the bone marrow do not have a poorer outlook than those without bone marrow involvement.     

Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix

PURPOSE: To compare the effects of concurrent administration of cisplatinum (40 mg/m(2)/weekly) with radiation therapy (C-RT) to those induced by radiation therapy alone (RT) on the immune function of patients with locally advanced cervical cancer. METHODS AND MATERIALS: In 8 prospectively randomized patients (i.e., 4 receiving RT vs. 4 receiving C-RT), lymphocyte populations including CD3+, CD4+ and CD8+ T-cell subsets, B cells (CD19+) and natural killer cells (CD56+, CD16+, CD3-) were studied before, during, and after therapy. Expression of the activation marker CD25 on CD3+ T cells, intracellular levels of perforin in CD8+ and CD56+ cells, and interferon-gamma (IFN-gamma) and IL-2 in CD4+ and CD8+ T cells was also measured. Finally, lymphoblast transformation and natural killer (NK) cytotoxic activity were assessed. RESULTS: Both RT and C-RT significantly decreased the mean absolute number of all lymphocyte subsets compared to pretreatment levels (p > 0.001). However, no differences were detected in the characteristics or the magnitude of the lymphopenia induced by the two treatments. Both RT and C-RT increased similarly the percentages of CD25-positive lymphocytes (p > 0.001), and significantly decreased PHA-induced T-cell lymphoblast transformation (p > 0.001) and NK cytotoxic activity against K562 cells (p > 0.001). The percentage of perforin-positive and CD8+ T cells was not altered during either treatment, whereas the percentage of perforin-positive and CD56+ cells was significantly reduced during both treatments, and correlated with reduced cytotoxicity against K562 cells. The percentages of CD8+ IFN-gamma+ and CD4+ IFN-gamma+ T cells as well as that of CD8+ IL-2+ and CD4+ IL2+ T cells were not significantly altered by C-RT compared to RT alone. Finally, with both regimens, NK cells and B-cell numbers showed a more rapid recovery than T-cell numbers. CONCLUSION: Administration of concurrent cisplatinum to radiation may synergistically increase cytotoxic effects of radiation on tumor cells but does not alter the magnitude and the characteristics of radiation-induced immunosuppression.     

112例淋巴系统恶性肿瘤骨髓免疫表型分析

背景与目的:淋巴细胞白血病和淋巴瘤骨髓侵犯的诊断以细胞形态学为基础,而免疫分型可通过获得肿瘤细胞分化和发育阶段的信息使淋巴系统恶性肿瘤的诊断更为准确,为临床合理治疗和预后判断提供重要的科学依据.本研究应用多参数流式细胞术(flow cytometry,FCM)探讨淋巴细胞白血病和非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)骨髓侵犯的免疫表型特点.方法:收集112例病理确诊NHL并伴骨髓侵犯和淋巴细胞白血病患者的骨髓标本.应用FCM检测肿瘤细胞的免疫表型.结果:45例前驱B淋巴母细胞白血病/淋巴瘤(precursor B lymphoblastic lymphoma/leukemia,B-ALL/LBL)主要表达CD19、CD10、TdT、CD34、HLA-DR和CD20;32例前驱T淋巴母细胞白血病/淋巴瘤(precursor T lymphoblastic lymphoma/leukemia,T-ALL/LBL)主要表达胞内CD3(cytoplasmic CD3,CyCD3)、CD7、CD5、TdT、膜表面CD3(surface CD3,sCD3)和HLA-DR.77例前驱淋巴细胞肿瘤中,28例(36%)有髓系抗原CD13、CD33的表达;9例(20%)B-ALL/LBL病例有CD20与CD34共同表达,28例(87.5%)T-ALL/LBL病例有CyCD3与TdT共同表达.成熟淋巴细胞肿瘤35例,其中17例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤主要表达CD19、CD20、CD5和HLA-DR,并有CD19与CD5共同表达.4例弥漫大B细胞性淋巴瘤主要表达CD19、CD20、CD10和HLA-DR.3例伯基特淋巴瘤主要表达CD19、CD10、CD20、SIgM.1例套细胞淋巴瘤表达CD5、CD19、CD20、HLA-DR.5例外周T细胞淋巴瘤(PTCL)主要表达sCD3、CD5、CD7、CD4或CD8.1例间变性大细胞淋巴瘤主要表达sCD3、HLA-DR.4例NK/T细胞肿瘤表达CD56、HLA-DR,也表达CD7或CD4或CD8.成熟淋巴细胞肿瘤不表达早期抗原如CD34、TdT.成熟淋巴细胞肿瘤可伴有髓系抗原CD13、CD33的表达.结论:淋巴系统恶性肿瘤侵犯骨髓采用形态学结合FCM免疫学分型可获得T、B细胞来源、肿瘤细胞分化阶段和异常抗原表达等参数,有助于临床诊断和微小残留病灶的检测.     

非霍奇金淋巴瘤患者血中CD+4 CD+25 T细胞/CD+4 T细胞比率意义初探

  目的 探讨非霍奇金淋巴瘤（NHL）患者外周血中CD+4 CD+25 T细胞／CD+4 T细胞比率的意义。方法 应用流式细胞技术检测15例健康人、41例初诊NHL患者、16例CTOP方案化疗后完全缓解后的NHL患者及25例化疗后未达到完全缓解的患者单位体积内外周血中CD+4 CD+25 T细胞数量和CD+4 T细胞,计算CD+4 CD+25 T细胞占CD+4 T细胞的比率。结果 初诊NHL患者CD+4 CD+25 T细胞／CD+4 T细胞的比率为（7.54±2.31）％,高于健康者的（4.13±1.25）％（P＜0.05）;化疗完全缓解后NHL患者外周血CD+4 CD+25 T细胞／CD+4 T细胞的比率为（6.26±2.28）％,低于初诊化疗前患者的（7.54±2.31％）（P＜0.05）。化疗后未达到完全缓解患者CD+4 CD+25 T细胞／CD+4 T细胞的比率为（7.85±2.12）％,高于化疗后完全缓解的患者的比率（6.26±2.28）％（P＜0.05）。结论 化疗缓解后的NHL患者外周血中CD+4 CD+25 T细胞／CD+4 T细胞的比率较化疗前及化疗未缓解的患者降低,提示CD+4 CD+25 T细胞／CD+4 T细胞的比率可能与NHL患者免疫功能及治疗效果有关。     

R-CHOP与CHOP方案治疗初治弥漫大B细胞型淋巴瘤在中国的多中心随机对照研究

背景与目的:CHOP化疗方案是目前治疗弥漫性大B细胞型非霍奇金淋巴瘤(non-HodgkinTslymphoma,NHL)的标准方案。利妥昔单抗(美罗华)作为一种针对CD20抗原表达阳性的B细胞的嵌合型单克隆抗体,对弥漫性大B细胞型淋巴瘤具有良好的疗效。在欧洲和美国,利妥昔单抗联合标准化疗方案治疗进展型NHL已经获得批准。本研究旨在比较利妥昔单抗加标准CHOP方案与标准CHOP方案治疗中国人CD20阳性的弥漫大B细胞型NHL患者的疗效和安全性。方法:2003年9月至2004年11月在全国9个研究中心进行,共有63例患者入组,其中CHOP组32例,R-CHOP组31例。所有入组患者均签署并提供知情同意书。CHOP组患者接受每3周为1个疗程共6个疗程的CHOP方案治疗;R-CHOP组患者在每个疗程开始的第1天联用利妥昔单抗的CHOP治疗方案。比较两组的完全缓解率、总体缓解率以及不良反应情况。结果:R-CHOP组和CHOP组的完全缓解率相似(41.9%vs.37.5%,P=0.719),而总体缓解率前者要高于后者(83.8%vs.65.6%,P=0.096),但无显著性差异。治疗期间CHOP组有21.9%的患者疾病进展,而R-CHOP组仅为3.2%,两组有显著性差异(P=0.026)。R-CHOP组和CHOP组的不良反应发生率相似(65.6%vs.67.7%),差异无显著性(P=0.859)。最常见的不良反应均为白细胞下降;R-CHOP组其次常见不良反应是发热和寒战,可能与输注利妥昔单抗有关。两组的临床相关毒副作用相似,差异无显著性。结论:利妥昔单抗联合CHOP方案治疗CD20阳性的弥漫大B细胞型NHL与单纯CHOP方案相比,能显著降低治疗失败率,同时并不增加化疗的毒副反应。     

弥漫大B细胞淋巴瘤中B7-H1临床表达水平分析

目的 对弥漫大B细胞淋巴瘤(DLBCL)中B7-H1的表达水平进行分析.方法 收集DLBCL患者病理活检或手术切除的肿瘤组织标本50例,另收集瘤周正常淋巴组织标本50例作为对照.采用Western Blot法检测B7-H1在瘤周正常淋巴组织与DLBCL肿瘤组织中的表达水平;采用流式细胞仪检测瘤周正常淋巴组织与DLBCL肿瘤组织中B7-H1和调节性T细胞(Treg)的表达水平.结果 Western Blot检测结果显示,B7-H1在DLBCL肿瘤组织与瘤周正常淋巴组织中均有表达,与瘤周正常淋巴组织比较,DLBCL肿瘤组织中B7-H1的表达水平较高.HLA-DR+CD14+巨噬细胞在DLBCL肿瘤组织中表达B7-H1的比例较瘤周正常淋巴组织高(P﹤0.05).与瘤周正常淋巴组织相比较,DLBCL肿瘤组织中(包括IPI值≥2分与IPI值﹤2分)pDC、Treg、mDC与调节性T细胞(CD4+/CD8+)的比例较高(P﹤0.05).结论 B7-H1在DLBCL患者的淋巴组织中呈高表达,提示B7-H1与淋巴瘤细胞的免疫逃逸有关,从而造成了DLBCL细胞免疫平衡的失调.     

Loss of B7.2 (CD86) and intracellular adhesion molecule 1 (CD54) expression is associated with decreased tumor-infiltrating T lymphocytes in diffuse B-cell large-cell lymphoma.

Tumor-infiltrating CD8+ T-lymphocytes (T-TILs) are thought to be relevant to immunosurveillance of several tumor types including B-cell non-Hodgkin's lymphoma. B- and T-lymphocyte interactions via cellular adhesion molecules (CAMs), recognition molecules (HLAs), and costimulatory molecules (CSMs) are necessary for optimal antigen-specific T-cell activation to occur and may be important in generating effective host T-TIL responses. We previously found that low T-TIL response (CD8+ T cells < 6%) correlates with statistically shorter relapse-free survival in patients with diffuse large-cell lymphoma (DLCL). We now extend our observations in 71 DLCL patients by analyzing malignant B-cell expression of the following molecules important in T-cell activation: (a) recognition molecules [MHC I (MAS and MCA) and MHC II (HLA-DR, -DP, -DQ)]; (b) CAMs [leukocyte function antigen 1 (CD11a and CD18) and intracellular adhesion molecule 1 (CD54)]; and (c) CSMs [B7.1 (CD80) and B7.2 (CD86)]. Eighteen patients (25%) had low a T-TIL response, and 53 patients (75%) had a high T-TIL response. Overall, expression of the MHC class H molecules HLA-DR and HLA-DQ was most conserved. The loss of B7.2 (P = 0.04), intracellular adhesion molecule 1 (P = 0.0004), MAS (P = 0.02), and HLA-DR (P = 0.0004) expression was significantly associated with decreased T-TIL response. In 100% of patients with low T-TIL responses, at least one HLA, CAM, or CSM was undetectable on the malignant B cells by immunohistochemical staining (mean number of molecules lost = 2.67). In contrast, 49% of patients with high T-TIL responses had no losses in HLA, CAM, or CSM expression (mean number of molecules lost = 0.89). The mean number of absent molecules (HLA, CAM, or CSM) was significantly associated with T-TIL response (P = 0.0001). We conclude that loss of HLA, CAM, or CSM expression on malignant B cells is associated with a poor host T-cell immune response. In addition, because patients with low T-TIL response had lost expression of multiple cellular adhesion, recognition, and costimulatory molecules, our results suggest that a combination of immunorestorative therapies may be required to generate effective antitumor T-cell responses in B-cell DLCL.     

Clinical significance of immunophenotype in diffuse aggressive non-Hodgkin's lymphoma

We performed a prospective study of the clinical significance of immunophenotype in 110 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by oncologists in the Nebraska Lymphoma Study Group between October 1982 and May 1986. All patients were immunophenotyped from biopsies performed before therapy was administered. The patients were treated with a uniform protocol of radiotherapy for minimal nonbulky, stage I or II disease (seven patients) or a single, six-drug chemotherapy regimen cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone (CAP-BOP) in patients with more extensive disease (103 patients). Ninety-one patients (83%) had B-cell lymphoma and 19 patients (17%) had T-cell lymphoma. The histologic diagnosis of diffuse mixed-cell lymphoma was significantly associated with T-cell immunophenotype (45% v 5%; P less than .001), and the diagnosis of diffuse large-cell lymphoma was significantly associated with B-cell immunophenotype (40% v 5%; P = .006). However, no significant difference in frequency of prognostic variables such as age, stage, systemic symptoms, tumor bulk, serum lactic dehydrogenase, or performance status was found between the B-cell and T-cell groups. Patients with B-cell NHL had a slightly higher complete remission rate (74% v 53%; P = NS), similar durability of complete remission (75% v 70% at 3 years; P = NS), and a slightly but not significantly better overall survival (50% v 41% at 3 years; P = NS). The slight advantage in response rate and survival for B-cell patients was related to a very poor outcome for patients with stage IV T-cell NHL. For patients with stage I to III disease, neither the complete remission rate (B-cell, 82% v T-cell, 91%; P = NS) nor overall survival (3-year survival for B cell, 58% v T cell, 73%; P = NS) were significantly different. However, with stage IV disease B-cell patients fared far better than those with T-cell NHL for both complete remission rate (67% v 0%; P = .002) and overall survival (3-year survival, 44% v 0%; P = .002). Immunophenotyping intermediate- and high-grade NHL allowed identification of a subgroup of patients who had a very poor prognosis with this treatment approach and for whom alternate therapy might be considered.