外周T细胞淋巴瘤患者中PD-1的表达对CD45RA+、CD45RO+T细胞的影响

目的:探讨外周T细胞淋巴瘤(PTCL)患者淋巴瘤组织中PD-1的表达与外周血中初始和记忆T细胞水平的关系.方法:20例PTCL患者采用免疫组化法检测淋巴瘤组织中PD-1的表达,采用流式细胞术检测CHOP方案化疗前后外周血中CD4+CD45RA+、CD4+CD45RO+、CD8+CD45RA+和CD8+CD45RO+T细胞的比例,分析PD-1的表达与T细胞亚群的关系.结果:PD-1、PD-L1蛋白在PTCL患者中表达升高,PD-1阳性患者疗效较差.PD-1阳性患者中CD4+T细胞、CD8+T细胞明显低于PD-1阴性患者;PD-1阴性组患者CD4+CD45RO+、CD8+CD45RA+、 CD8+CD45RO+T细胞明显高于PD-1阳性患者,差异有统计学意义.结论:PTCL患者中存在PD-1/PD-L1蛋白的表达异常,PD-1阳性患者存在更明显的T细胞免疫功能缺陷.     

Long-lasting decrease of CD4+/CD45RA+ T cells in HCL patients after 2-chlorodeoxyadenosine (2-CdA) treatment.

The CD45RA and CD45RO isoforms of the leukocyte common antigen identify functionally distinct CD4+ T cell subsets: CD4+/CD45RA+ cells which represent a more 'naive' stage of T cell compartment and CD4+/CD45RO+ 'memory' cells. Phenotypic and functional abnormalities in T cell compartment have been frequently reported in patients with hairy cell leukemia (HCL) and, in more recent studies, a significant reduction in the absolute number of CD4+ lymphocytes bearing the CD45RO antigen has also been recorded. In our study we evaluated the CD45RA and CD45RO expression on CD4+ T cells by three-color staining in flow cytometry in 38 HCL patients, 19 untreated and 19 previously treated with 2-chlorodeoxyadenosine (2-CdA), administered at a daily dose of 0.1 mg/kg c.i. for 7 days. In HCL untreated patients, the proportion and the absolute number of CD4+/CD45RA+ and of CD4+/CD45RO+ T cell subsets were similar to normal controls. In contrast, HCL patients at 3-5 years by the end of treatment with 2-CdA, together with a reduction in the absolute number of CD4+ T cells, showed a persistent and significant decrease in the proportion and absolute number of CD4+/CD45RA+ cells as compared with both untreated HCL patients and normal controls (41 +/- 16% vs 57 +/- 14% and vs 65 +/- 7%) (P = 0.01 and 0.0001) and (0.201 +/- 0.137 x 10(9)/l vs 0.549 +/- 0.238 x 10(9)/l and vs 0.696 +/- 0.078 x 10(9)/l) (P = 0.00009 and P = 0.00001). In addition, together with the reduction of CD4+/CD45RA+ cells, we recorded a concomitant increase in the proportion of the CD4+/CD45RO+ cells as compared to untreated HCL patients and normal controls (62 +/- 16% vs 47 +/- 15% and vs 42 +/- 12%) (P = 0.08 and 0.02). These findings may suggest that CD4+/CD45RA+ cells are more sensitive than CD4+/CD45RO+ to the toxic effect of 2-CdA.     

Immune parameters in multiple myeloma patients: influence of treatment and correlation with opportunistic infections

The present study evaluated cellular and humoral immune parameters in myeloma patients, focusing on the effect of treatment and the risk of opportunistic infections. Peripheral blood lymphocyte subsets and serum levels of nonmyeloma immunoglobulins (Ig) were analysed in 480 blood samples from 77 myeloma patients. Untreated myeloma patients exhibited significantly reduced CD4+/45RO+, CD19+, CD3+/HLA-DR+, and natural killer (NK) cells, as well as nonmyeloma IgA, IgG and IgM. Conventional-dose chemotherapy resulted in significantly reduced CD4+ and even further decline of CD4+/CD45RO+ and CD19+ cells, most notably in relapsed patients. Additional thalidomide treatment had no significant effects on these parameters. Following high-dose chemotherapy (HD-CTX), prolonged immunosuppression was observed. Although CD8+, NK, CD19+ and CD+/CD45RO+ cells recovered to normal values within 60, 90, 360 and 720 days, respectively, CD4+ counts remained reduced even thereafter. Nine opportunistic infections were observed, including five cytomegalovirus (CMV) diseases, one Pneumocystis carinii pneumonia (PCP) and three varicella zoster virus infections with CMV diseases and PCP occurring exclusively after HD-CTX. Opportunistic infections were correlated with severely reduced CD4+, as well as CD4+/CD45RO+ and CD19+ counts. Thus, myeloma patients display cellular and humoral immunodeficiencies, which increase following conventional as well as HD-CTX, and constitute an important predisposing factor for opportunistic infections.     

结直肠癌患者外周血中CD4+CD45RA+ T和CD4+CD45RO+ T细胞的变化及其意义

目的 探讨外周血中CD4 CD45RA T细胞和CD4 CD45RO T细胞在结直肠癌中的变化及其临床意义。方法 采用流式细胞术检测60例结直肠癌患者手术前、术后1个月和3个月时,外周血的CD4 T细胞、CD4 CD45RA T细胞和CD4 CD45RO T细胞的比例。选取健康查体人群10例作为对照。结果 结直肠癌患者的CD4 T细胞与健康人群相比无差异。CD4 CD45RO T细胞比例明显增高,术后有显著下降,DukesA、B期患者尤其明显;而CD4 CD45RA T细胞比例正好相反。结论 CD4 CD45RA T细胞和CD4 CD45RO T细胞在肿瘤免疫中起重要作用,其表达同结直肠癌的分期和预后有密切关系。     

Differential depression of lymphocyte subsets according to stage in stomach cancer

Lymphocyte surface markers were determined in the peripheral blood lymphocytes (PBL) in 31 stomach cancer patients (15 males and 16 females) and 47 controls (20 males and 27 females) using an indirect immunofluorescence technique. The monoclonal antibodies used were Leu 2a (CD8, suppressor/cytotoxic T cells), Leu 3a (CD4, inducer/helper T cells), Leu 4 (CD3, pan T reagent), Leu 11 (CD16, natural killer cells) and Leu 12 (CD19, B cells). The numbers of PBL, CD3+, CD4+, CD8+, CD16+ and CD19+ cells significantly decreased and the CD4:CD8 value increased in patients with stomach cancer compared to those in healthy volunteers. In stage I, PBL, none of the PBL subsets nor the CD4:CD8 value were significantly different from those of the controls. In stage II, the numbers of PBL, CD3+, CD4+ and CD8+ cells decreased. In stage III, the CD19+ cells decreased in addition to the decreased subsets in stage II. In stage IV, PBL and all subsets measured decreased. The CD4:CD8 value showed significant increases in stages II, III and IV, because the CD8+ cells decreased to a greater extent than did the CD4+ cells. Changes in the subsets were analyzed with regard to age, sex, performance status and smoking history, no significant relation being observed between these factors and lymphocyte subsets. From the present study, we have demonstrated that lymphocyte subsets were differentially depressed in the order of T cells, B cells and natural killer cells, with progression of the stage of disease.     

An Analysis of Circulating CD4 Lymphocyte Subpopulations in B-Cell Chronic Lymphocytic Leukaemia

The distribution of circulating CD4 lymphocyte subpopulations determined by reactivity with monoclonal antibodies anti-2H4 (CD45RA), anti-UCHL1 (CD45RO), anti-4B4 (CD29) and anti-Leu8, and analysed by dual colour immunofluorescence flow cytometry is described in a series of patients with B-CLL and in age-matched control subjects. The percentages and absolute numbers of CD4 cells reactive with anti-CD45RA, anti-CD45RO and anti-CD29 reagents were similar in the patient and control groups. In contrast, CD4+ Leu8+ cells (percentages and absolute numbers) were significantly reduced in B-CLL patients resulting in an inversion of the normal CD4+ Leu8+ :CD4+Leu8- ratio. The patients' clinical or therapeutic status did not appear to influence the levels of the respective CD4 subpopulations; nor was evidence of hypogammaglobulinaemia associated with specific numerical alterations in any of the CD4 subpopulations studied. It is proposed that, in B-CLL, the alterations in the CD4Leu8 subpopulations are associated with the disease process, whereas the distributions of CD4+CD45RA+, CD4+ CD45RO+ and CD4+ CD29+ cells reflect the normal physiological levels of these subpopulations in elderly subjects.     

Effector, memory and naïve CD8+ T cells in peripheral blood and pleural effusion from lung adenocarcinoma patients

The proportions of na?ve, memory and effector CD8+ T cells in peripheral blood and pleural effusion from lung adenocarcinoma patients were studied. CD8+ T subsets were identified by using a combination of the following antibodies: anti-CD45RA, anti-CD45RO, anti-CD27 and anti-CD28, as well as antibodies to other markers. Fas-positive cells were determined in each CD8+ T subset. Also, the intracellular cytokine patterns of CD4+ and CD8+ lymphocytes from pleural effusion were analysed. In na?ve, memory and effector CD8+ T subsets no significant differences were observed in peripheral blood between healthy donors and cancer patients. In contrast, a high proportion of cells with memory phenotype (CD45RA-CD45RO+CD27+CD28+) and a low proportion of cells with effector phenotype (CD45RA+CD45RO-CD27-CD28-) were found in pleural effusion with respect to peripheral blood (P<0.001). The altered proportions of CD8+ T subsets in pleural effusion were not mediated by type 2 cytokines produced by CD4+ or CD8+ lymphocytes. In the effector CD8+ T subset, from peripheral blood as well as from pleural effusion, a low percentage of perforin-expressing cells was observed compared to granzyme A-expressing cells. Additionally, a high percentage of na?ve CD8+ T cells expressing Fas was found. Our data suggest that: (i) terminal-differentiation process of CD8+ T cells is blocked, and (ii) early Fas-expression in CD8+ T cells, which was reflected even in peripheral blood, may lead to apoptosis of na?ve cells when they reach the effector stage. All these processes may contribute to the inadequate antitumour immune response found in lung carcinoma patients.     

Natural killer and lymphokine-activated killer activities in stomach cancer patients with special emphasis on the effect of 5-fluorouracil, adriamycin and mitomycin-C chemotherapy

The cytotoxicities of peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells were studied to evaluate the effect of chemotherapy on cellular immunity, in 18 patients with unresectable stomach cancer before and after chemotherapy with 5-fluorouracil, adriamycin and mitomycin-C (FAM), and in 21 healthy volunteers. LAK cells were generated in vitro by culturing PBL with 100 U recombinant human interleukin-2 (rH-IL-2)/ml for 72 h. K562 (human myelogenous leukemia), MKN-45 (human stomach adenocarcinoma) and PC-14 (human pulmonary adenocarcinoma) were used as target cells. The cytotoxicity of PBL to K562 and MKN-45 was suppressed in patients with stomach cancer before chemotherapy, compared with that in healthy volunteers (P less than 0.05). The cytotoxicity of LAK cells was significantly higher to all three cell lines tested than that of PBL in both the healthy volunteers and stomach cancer patients (P less than 0.01); however, a lower level of LAK activity was generated in patients with cancer compared to that in the healthy volunteers. FAM therapy did not suppress the cytotoxicities of PBL and LAK cells. The surface markers of PBL and LAK cells were measured, demonstrating that there was no significant change in the percentage of lymphocytes with CD3+, CD4+, CD8+, CD16+ or CD19+ after chemotherapy. The ratios of CD4+ to CD8+ cells in PBL and LAK cells were also not significantly changed after chemotherapy. In the present study, we have demonstrated that the PBL of stomach cancer were defective in generating LAK activity compared to those of controls, but the LAK activity generated from PBL receiving chemotherapy was similar to that from PBL without chemotherapy in stomach cancer patients.     

化疗对中晚期非小细胞肺癌患者淋巴细胞亚群的影响

目的探讨NSCLC患者在化疗前后淋巴细胞亚群含量的变化及临床意义。方法采用流式细胞仪技术,分别对治疗组和对照组外周血淋巴细胞亚群进行检测计数。结果 76例NSCLC患者CD3＋、CD4＋、NK细胞的数量以及CD4＋/CD8＋比值均明显低于健康人群,其CD8＋细胞的比例明显高于健康人群,差异具有统计学意义（P〈0.05）。化疗后CD3＋、CD4＋、CD4＋/CD8＋、NK较化疗前升高（P〈0.05）;CD8＋化疗前后差异无统计学意义（P〉0.05）。结论 NSCLC患者机体的免疫状态与病情发展、临床分期密切相关,化疗可明显改善NSCLC患者机体的免疫功能。     

培美曲塞联合含铂方案化疗对非小细胞肺癌患者外周血淋巴细胞表型的影响

目的探讨培美曲塞（pemetrexed）联合顺铂（cisplatin）或卡铂（carboplatin）治疗方案对非小细胞肺癌患者外周血淋巴细胞表型的影响。方法45例经病理学或细胞学确诊的非小细胞肺癌患者,采用培美曲塞500 mg/m2,第1天静脉滴注;顺铂25 mg/m2,第1～3天或卡铂按AUC=5计算剂量,第2天静脉滴注,21天为一周期,毎例患者至少治疗2周期,有可测量病灶者进行疗效评价。应用流式细胞仪检测化疗前和化疗后第7天外周血CD3+、CD4+、CD8+、CD16+56+、CD19+细胞的百分率和CD4+/CD8+比值。结果非小细胞肺癌患者经培美曲塞联合含铂方案化疗后CD4+、CD4+/CD8+、CD16+56+较化疗前升高（P=0.032）,CD3+、CD8+、CD19+化疗前后差异无统计学意义（P>0.05）;临床分期为ⅢB～Ⅳ期的患者化疗前CD3+、CD4+、CD4+/CD8+和CD16+56+较ⅠB～ⅢA期患者低（P=0.029）,化疗后两者比较差异无统计学意义（P>0.05）;化疗有效者CD3+、CD4+、CD4+/CD8+比值均显著增高（P=0.008）。结论非小细胞肺癌患者,尤其是晚期患者机体免疫功能低下。培美曲塞联合含铂方案化疗打破了原有的抗肿瘤免疫抑制状态,机体有可能通过免疫重建增强抗肿瘤免疫应答。     

晚期肺腺癌患者一线化疗后T淋巴细胞亚群变化及临床意义

背景与目的机体的免疫功能异常与恶性肿瘤的发生、发展、转移及预后密切相关。T淋巴细胞亚群是反映细胞免疫功能的重要指标之一。本实验研究晚期肺腺癌患者一线化疗后外周血T淋巴细胞数量的动态变化,探讨化疗后机体免疫状态变化的动态过程,为制定化疗联合免疫治疗方案提供实验依据。方法 49例经病理学确诊的IIIb期-IV期肺腺癌患者,与33例正常人比较外周血T淋巴细胞数量。然后患者随机进入2个实验组,分别采用培美曲塞、顺铂联合方案及多西他赛、顺铂联合方案化疗,应用流式细胞仪检测化疗前后不同时间点淋巴细胞的组成。结果肺癌患者的CD3+、CD3+CD4+、CD4+CD25+等T细胞的数量与健康对照组比较存在差异,P值分别为0.012,0.034和0.006;化疗后第4天及第7-10天CD3+、CD3+CD4+比例升高,至第21天逐渐恢复至治疗前水平;2个化疗组比较CD3+细胞比例均升高,而培美曲塞组第4天CD3+、CD3+CD4+、CD4+/CD8+升高,CD3+CD8+及CD8+CD28-比例降低,差异均具有统计学意义。部分缓解患者较早期疾病进展患者的第4天及第7-10天CD3+CD4+细胞升高;第4天CD3+CD8+、CD8+CD28-细胞降低。结论晚期肺腺癌患者免疫功能处于抑制状态。化疗后第4天免疫功能得到一定程度恢复,至第21天恢复至治疗前水平。培美曲塞似乎对化疗后短期内免疫功能的改善有更明显的作用。化疗后免疫格局的改变可能与预后有关。     

肺癌患者淋巴细胞亚群在外周血中的表达及其与预后的关系

背景与目的肺癌是最常见的恶性肿瘤之一,本研究旨在探讨肺癌患者外周血中淋巴细胞亚群的表达及与预后的关系。方法采用流式细胞仪检测221例原发性肺癌首诊患者外周血淋巴细胞亚群CD3+、CD4+、CD8+、CD4+/CD8+、CD19+、CD25+、CD44+及NK细胞所占比例,并与96例健康人的血标本对比,结合临床及随访资料进行统计分析。结果与健康对照组对比,肺癌患者淋巴细胞亚群8项指标中CD3+及CD8+明显低于健康对照组,CD4+/CD8+、CD19+、CD25+、CD44+及NK细胞明显高于健康对照组(P<0.05)。与非小细胞肺癌(non-small cell lung cancer,NSCLC)相比,小细胞肺癌(small cell lung cancer,SCLC)的CD8+明显升高而CD4+和CD4+/CD8+明显下降(P<0.05)。化疗后与化疗前相比CD3+明显上升,NK细胞、CD19+及CD44+明显下降(P<0.05),其中CD44+在化疗后表达不升高者有生存优势(P=0.021),而其余3项指标与患者预期生存无关。结论肺癌患者外周血淋巴细胞亚群普遍发生改变,CD44+在化疗后的改变可能与预后相关。     

Decreased numbers of CD4+ T lymphocytes in peripheral blood after treatment of childhood acute lymphoblastic leukemia

Treatment-related immunosuppression in patients with acute lymphoblastic leukemia (ALL) is associated with increased susceptibility to infectious diseases, also after the treatment. The aim of the present study was the detailed evaluation of T lymphocyte subsets in peripheral blood in children after treatment of ALL. All children were treated according to the BFM 90 protocol. The patients were divided into 5 groups of 30 children in each, depending on the time from cessation of the ALL treatment. A control group consisted of 30 healthy children subjected to elective "1-day" surgery. The children's age ranged from 6 to 18 years. The examinations were performed in FACScan flow cytometer with the use of wide set of monoclonal antibodies: CD3, CD4, CD8, TCRalphabeta, TCRgammadelta, CD19, CD25, CD45RA, CD45RO, CD69, HLA-DR, CD16 and CD56, which particularly allowed detailed analysis of T lymphocytes. The results showed that most parameters in children 1 year after ALL treatment completion were similar to healthy children. However, we observed persistently low CD4+ T cell numbers, both CD45RA+ as well as CD45RO+ subsets as compared to the control group. This might reflect decreased regenerative potential of immunological system in children 1 year after ALL treatment.     

外周血T淋巴细胞亚群检测在胃癌病情监测及预后评价中的意义

目的：探讨外周血T淋巴细胞亚群检测在胃癌病情监测及预后评价中的价值。方法选择100例胃癌患者作为胃癌组,患者采用mFOLFOX6方案,2周为1个疗程,每位患者化疗4个疗程以上。另选择同期在医院体检的健康人群80例作为对照组,采用流式细胞仪技术检测两组外周血T淋巴细胞亚群水平。结果化疗前胃癌组外周血CD3+、CD4+、CD4+/CD8+显著低于对照组,CD8+显著高于对照组,差异有统计学意义（P﹤0.01）。Ⅰ～Ⅱ期胃癌患者外周血CD3+、CD4+、CD4+/CD8+显著高于Ⅲ～Ⅳ期,CD8+显著低于Ⅲ～Ⅳ期,差异有统计学意义（P﹤0.01）。不同疗效的胃癌患者化疗前外周血T淋巴细胞亚群水平比较差异无统计学意义（P﹥0.05）,化疗后CR+PR组、SD组、PD组外周血CD3+、CD4+、CD4+/CD8+显著降低,CD8+显著上升,差异有统计学意义（P﹤0.01）,且CR+PR组外周血CD3+、CD4+、CD4+/CD8+显著高于SD组和PD组,CD8+显著低于SD组和PD组,差异有统计学意义（P﹤0.01）。结论通过检测血清外周血T淋巴细胞亚群水平能够有助于评估胃癌的病情和预后。     

The effect of short-course high-dose methylprednisolone on peripheral blood lymphocyte subsets in children with acute leukemia during remission induction treatment

We have previously demonstrated a favorable effect of high-dose steroid in the treatment of children with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). This study was performed to determine the effect of short-course high-dose methylprednisolone (HDMP) treatment on the peripheral blood (PB) T lymphocyte subsets, and blast cells, during remission induction treatment in 23 children with newly diagnosed acute leukemia (16 with ALL, seven with AML). All patients were administered HDMP as a single daily oral dose of 30mg/kg for the first 4 days of induction therapy. The number of PB lymphocyte subsets (CD3, CD4, CD8, CD16+56, CD45RA, and CD45RO) were determined by flow cytometry before and after 4 days of HDMP treatment. While the number of PB blast cells significantly decreased, the absolute number of T lymphocytes expressing CD3, CD4, CD8, CD45RA and the absolute number of CD16+56 (natural killer) cells increased in all patients. We suggest that the beneficial effects of HDMP in the induction treatment of acute leukemia may occur partly due to an increase in the number of PB T lymphocyte subsets. A study randomly assigning patients to treatment with either conventional therapy or HDMP may provide further information.     

全麻复合硬膜外麻醉对肺癌根治术患者外周血T细胞亚群及NK细胞活性的影响

目的探讨全麻复合硬膜外麻醉对肺癌根治术患者外周血T细胞亚群及NK细胞活性的影响。方法收集接受肺癌根治术的84例患者的病历资料,按照患者所行麻醉方式的不同对其进行分组,单纯行全麻者42例归为对照组,行全麻复合硬膜外麻醉者42例纳入观察组,分析不同麻醉方式对患者外周血T细胞亚群及NK细胞活性影响的差异性。结果术后24 h观察组与对照组患者的CD3^+、CD4^+、CD8^+、CD4^+/CD8^+、NK细胞水平均较术前明显降低,且术后24 h相比对照组患者的CD3^+、CD4^+、CD8^+、CD4^+/CD8^+、NK细胞水平,观察组患者以上指标水平明显更高(P<0.05)。术后1周2组患者的CD3^+、CD4^+、CD8^+、CD4^+/CD8^+水平与术前相比并无明显差异(P>0.05),但NK细胞水平较术前明显降低(P<0.05),且术后1周相比对照组患者,观察组患者的NK细胞水平更高(P<0.05)。观察组患者的术后苏醒时间、术后拔管时间、自主呼吸恢复时间均明显短于对照组患者,2组差异有统计学意义(P<0.05)。结论相比单纯全麻,全麻复合硬膜外麻醉对肺癌根治术患者外周血T细胞亚群及NK细胞活性的影响更小,有助于患者术后的恢复。     

参麦注射液联合TP化疗方案对乳腺癌术后患者的疗效观察及生存质量的影响

目的探讨参麦注射液联合TP化疗方案对乳腺癌术后患者的疗效及生存质量的影响。方法将80例患者按照随机数字表法随机分为2组,分别为对照组（n=39）和观察组（n=41）。对照组采用TP化疗方案治疗,观察组在对照组基础上结合参麦注射液治疗。对比分析2组治疗前后Karnofsky评分变化、近期疗效、T淋巴细胞亚群变化。结果2组Karnofsky评分治疗后较治疗前显著增加（P〈0.05）;观察组Karnofsky评分治疗后显著高于对照组（P〈0.05）;观察组有效率（63.41%）显著高于对照组（35.90%）（P〈0.05）。观察组CD3^＋、CD4^＋、CD4^＋/CD8^＋治疗后较治疗前明显增加,CD8^＋较治疗前明显减少,且具有统计学差异（P〈0.05）;观察组CD3^＋、CD4^＋、CD4^＋/CD8^＋治疗后显著高于对照组,而CD8^＋治疗后显著低于对照组（P〈0.05）。结论参麦注射液联合TP化疗方案对乳腺癌术后患者近期疗效显著,可明显提高患者生存质量。     

Tumor infiltrating lymphocytes and PD-L1 expression in brain metastases of small cell lung cancer (SCLC)

Brain metastases (BM) are frequent in small cell lung cancer (SCLC). Novel insights into their pathobiology are needed for development of better therapies. We investigated tumor-infiltrating lymphocyte (TIL) subsets (CD3+, CD8+, CD45RO+, FOXP3+ and PD-1+) and expression of PD-L1 in a series of 32 SCLC BM specimens and four matched primary tumor specimens using immunohistochemistry. 30/32 (93.8?%) BM specimens showed TIL infiltration. CD3+ TILs were observed in 30/32 (93.8?%) BM specimens, CD8+ TILs in 25/32 (78.1?%), CD45RO+ TILs in 15/32 (46.9?%), FOXP3+ TILs in 15/32 (46.9?%) and PD-1+ TILs in 1/32 (3.1?%) BM specimens. Patients with infiltration of CD45RO+ TILS had a significantly longer median survival time (11 months; 95?% CI 0.000–26.148) as compared to patients without the presence of CD45RO+ TILs (5 months; 95?% CI 0.966–9.034; p?=?0.007; log rank test). Membranous PD-L1 on tumor cells was observed in 24/32 (75.0?%) BM specimens, with 11/32 (34.4?%) cases showing PD-L1 expression in over 5?% of viable BM tumor cells. PD-L1 expression on TILs was seen in 8/32 (25.0?%) and on tumor infiltrating macrophages in 9/32 (28.1?%) cases. Patients with PD-L1 expression on TILs presented with improved survival prognosis (6 versus 29 months; p?=?0.002; log rank test). Among matched primary tumors, all (4/4; 100?%) specimens showed TIL infiltration, while PD-L1 expression found in only 1/4 (25.0?%) specimen. TIL infiltration and PD-L1 expression are commonly found in SCLC BM and presence of CD45RO+ memory T-cells and PD-L1+ TILs in SCLC BM seem to associate with favorable survival times. Our data suggest an active immune microenvironment in SCLC BM that may be targetable by immune-modulating drugs.     

Cd4+ T-cell immune response to large B-cell non-Hodgkin's lymphoma predicts patient outcome.

PURPOSE: Previous studies in patients with non-Hodgkin's lymphoma (NHL) and other malignancies have suggested that the presence of host infiltrates in the tumors of these patients may predict a better outcome. This study was undertaken to determine the prognostic importance of the presence of T cells in the biopsy specimens of patients with B-cell NHL. PATIENTS AND METHODS: Seventy-two patients with diffuse large B-cell NHL were prospectively evaluated at a single institution between 1987 and 1994. The percentage of CD3+, CD3+/HLA-DR+, CD4+, CD8+, and natural killer cells was determined by flow cytometry in the pretreatment diagnostic biopsy specimen and correlated with patient outcome. RESULTS: An increase in the percentage CD4+ T cells in the pretreatment tumor biopsies significantly correlated with patient outcome. The percent of CD4+ T cells was also highly correlated with CD3+/HLA-DR+, CD45RO+, and low L-selectin (CD62L) expression, indicating that the CD4+ T cells are activated memory T-helper cells. Those patients with increased numbers of CD4+ T cells, compared with other patients, had a significantly longer 5-year failure-free survival (72% v 43%, respectively; P =.04), as well as a significantly longer 5-year overall survival (65% v 38%, respectively; P =.05). When evaluated in a multivariate model, the International Prognostic Index and more than 20% infiltrating CD4+ T cells in the pretreatment biopsy were significant independent predictors of relapse-free and overall survival. CONCLUSION: The presence of increased numbers of activated CD4+ cells in the area of B-cell diffuse large-cell NHL predicts a better prognosis. This finding provides a strong rationale for the investigation of cellular immunotherapy in B-cell NHL.     

免疫细胞治疗联合化疗治疗晚期卵巢癌患者的疗效及对细胞免疫的影响

目的:观察免疫细胞治疗联合化疗治疗晚期卵巢癌患者的疗效及对细胞免疫的影响。方法:2014年1月至2016年12月在普陀区人民医院收治的Ⅳ期卵巢癌患者102例,按照随机数字法将患者分为观察组和对照组,每组各51例,对照组予以传统化疗,观察组在对照组的基础上予以免疫细胞治疗。观察两组的疗效、治疗前后总生命质量评分（TQLS）、抑郁自评量表评分（SDS）、焦虑自评量表(SAS)、白介素（IL）-6、IL-10、干扰素（INF）-γ、IL-2、CD3+、CD4+、CD8+和CD4+/CD8+水平的变化。结果:观察组的总有效率为66.67%明显高于对照组的43.14%,两组比较差异有统计学意义（P<0.05）。两组治疗前TQLS、SDS和SAS评分差异无统计学意义（P>0.05）,治疗后TQLS、SDS和SAS评分较治疗前明显降低（P<0.01）,而观察组降低的更明显（P<0.01）。术前IL-6、IL-10、INF-γ、IL-2、CD3+、CD4+、CD8+和CD4+/CD8+水平差异无统计学意义（P>0.05）,治疗后观察组的IL-6、IL-10和CD8+水平较治疗前明显降低（P<0.01）,对照组较治疗前明显升高（P<0.01）,观察组较对照组明显降低（P<0.01）;观察组的INF-γ、IL-2、CD3+、CD4+和CD4+/CD8+水平较治疗前明显升高（P<0.01）,对照组较治疗前明显降低（P<0.01）,而观察组较对照组明显升高（P<0.01）。结论:免疫细胞治疗联合化疗对晚期卵巢癌患者的疗效显著,具有提高生活质量,缓解患者的焦虑和抑郁,与机体的细胞免疫提高有关。