自体瘤苗治疗实体肿瘤对免疫功能的影响

目的:探讨自体瘤苗治疗实体瘤的临床应用价值及对患者免疫功能的影响。方法:46例瘤苗组实体瘤术后患者应用自体瘤苗,并与对照组20例进行比较,对其疗效进行判断评价,检测治疗前后外周血T细胞亚群CD3+、CD4+、CD8+、CD4+/CD8+比值变化及NK细胞的活性、IgA、IgG、IgM免疫球蛋白水平。结果:瘤苗组治疗后CD3+,CD4+、CD4+/CD8+、免疫球蛋白水平较治疗前显著增加(P<0.05),对照组无明显变化(P>0.05)。近期随诊也表明瘤苗组效果明显优于对照组(P<0.01)。结论:自体瘤苗疗法可以恢复实体肿瘤患者受损的细胞免疫功能,提高治疗效果。     

NDV/β-榄香烯自体瘤苗对消化道肿瘤患者T细胞不同亚群平衡的影响

目的:探讨新城鸡疫病毒及β-榄香烯联合处理的自体瘤苗对消化道肿瘤患者T细胞不同亚群免疫平衡的影响.方法:对80例消化道肿瘤患者术后进行自体瘤苗治疗,检测患者手术前、免疫治疗结束后外周血中CD4 、CD8 、CD4 /CD8 比值变化,以及Th1类细胞因子(IL-2、IFN-γ)和Th2类细胞因子(IL-4、IL-10)的变化.结果:瘤苗治疗后,患者外周血T细胞亚群CD4 、CD8 、CD4 /CD8 比值均发生了较明显变化,与治疗前比较差异有显著性(P＜0.05), 与正常对照组比较差异无显著性 ;治疗后IL-2 、IFN-γ水平上升,而IL-4 和IL-10水平下降,与治疗前比较差异有显著性,与正常对照组比较差异无显著性.结论:自体肿瘤疫苗免疫疗法有助于恢复免疫系统平衡,增强机体抗肿瘤免疫能力;纠正肿瘤患者Th1/Th2偏离状态.     

放射治疗对鼻咽癌患者细胞免疫功能的影响

应用抗人淋巴细胞单克隆抗体检测32例鼻咽癌患者放疗前、后外周血T淋巴细胞亚群，并与12例非癌人群（对照组）进行对比。结果：鼻咽癌患者OKT3、OKT4及OKT4/OKT8值与对照组相比明显降低，OKT8值显著上升（P＜0．05）；放疗后OKT3、OKT4及OKT4/OKT8值进一步下降，OKT8进一步升高（P＜0．01）。提示鼻咽癌患者细胞免疫功能低下，放射治疗可进一步抑制鼻咽癌患者的细胞免疫功能。     

人结肠癌主动特异性免疫治疗的初步研究

目的:探讨自体肿瘤疫苗的作用机制及临床意义。方法:50例进展期结肠癌病人术后,以自体肿瘤细胞疫苗辅助主动免疫治疗。术后第4周开始免疫接种(共4次,每次间隔7~10天);接种前3天及第4次接种后1周,采集外周血。采集血清监测血清IFN-γ、IL-10水平;用PPD及自体肿瘤抗原做皮肤迟发型过敏试验(DTH),48小时后测量红斑、硬结大小(mm);对DTH反应部位皮肤活检,用免疫组化染色,了解局部免疫活性细胞浸润;临床随访。结果:自体肿瘤细胞疫苗治疗后:血清IFN-γ水平升高,由(6.01±2.30)pg/ml升至(12.98±4.65)pg/ml;而IL-10水平由(19.80±10.15)pg/ml降至(8.92±4.60)pg/ml,差异有非常显著性(P<0.05);治疗前后病人对自体肿瘤抗原的特异性DTH反应明显增强(P<0.01);DTH反应部位,CD8 T细胞、CD4 T细胞及DC细胞浸润明显增多;病人耐受性良好,无溃疡等严重副作用发生;随访结果显示:术后辅助自体肿瘤疫苗主动特异性免疫治疗,可延长结肠癌病人的无瘤生存时间,降低复发率及死亡率。结论:自体肿瘤疫苗可激发病人特异性细胞介导的免疫反应;可改善肿瘤病人的抗瘤免疫反应;自体肿瘤疫苗主动特异性免疫治疗,对于杀灭残留癌细胞、抗转移及复发有重要作用。     

维甲酸对大肠癌患者T淋巴细胞亚群及集落形成的影响

背景与目的：维甲酸是维生素A的衍生物,可完全或部分阻断实验性大肠癌的癌变过程,降低大肠癌的发生率。但对大肠癌患者T淋巴细胞亚群及集落形成的影响,尚未见报道。本文的目的是探索维甲酸对大肠癌患者免疫功能的影响。方法：对40例大肠癌患者进行前瞻性研究,所有患者均行大肠癌根治术。将病例随机分为维甲酸治疗组和对照组（每组20例）,分别在术前及术后检测两组患者外周血中T淋巴细胞亚群、T淋巴细胞集落形成和血清免疫球蛋白水平。结果：（1）两组术中OKT3无显著性变化,而OKT4、T4／T8的增加及OKT8的下降有统计学意义（P＜0．05）。两组对比,维甲酸治疗组OKT3、OKT4及T4／T8显著高于对照组,OKT8差异则无统计学意义（P＞0．05）。（2）维甲酸治疗组患者T淋巴细胞集落数显著低于正常人T淋巴细胞集落数,但却显著高于对照组大肠癌患者T淋巴细胞集落数（P＜0．05）。结论：大肠癌根治术后应用维甲酸,可提高患者的细胞免疫及体液免疫功能,促进免疫抑制状态的恢复。     

DC-CIK过继性细胞免疫治疗对卵巢癌患者的预后及免疫功能的影响

目的:探讨自体DC-CIK细胞疗法改善卵巢癌患者的预后及免疫功能的能力。方法:回顾性分析2014年1月至2015年12月在中国医科大学附属盛京医院均接受了规范的初始治疗、达到完全缓解（CR）的卵巢癌患者90例。分析比较其基本条件、免疫指标、无瘤生存时间及不良反应。结果:经DC-CIK生物免疫治疗的患者外周血CD3+、CD4+细胞百分率,CD3+、CD8+细胞百分率及CD4+/CD8+比值均上升,NK细胞即CD16+、CD56+细胞增多,同时随着疗程数的增多,升高的更加明显（P<0.05）。一线治疗后,单纯观察组平均无瘤生存时间为15.88±2.7个月明显少于DC-CIK生物免疫治疗组的22.5±4.13个月（P=0.039）。其中使用DC-CIK生物免疫治疗疗程≥5程的平均无瘤生存时间为27.25±4.53个月明显高于DC-CIK生物免疫治疗疗程≤4程的19.69±2.81个月,两者相比差异无明显统计学意义（P=0.412）。所有患者DC-CIK细胞治疗后血常规及肝肾功能检测与治疗前及单纯观察组患者相比无明显变化,也未见明显不良反应。结论:DC-CIK免疫治疗提高卵巢癌患者的免疫反应,改善卵巢癌患者预后,未见明显不良反应。     

乌苯美司对肺鳞癌化疗患者免疫功能的影响

目的 评价乌苯美司对肺鳞化疗患者免疫功能的影响。方法 将56例未手术肺鳞癌患者按3：2的比例随机分入试验组（34例）及对照组（22例）,患者均接受CAP方案化疗,每21天为1周期,共3个周期;试验组加服乌苯美司30mg,每日1次,共6个月。分析化疗疗效,观察治疗前、治疗后3、6个月淋巴细胞绝对计数（LC）、OKT4／T8、NK细胞活性、血清IL－2、SIL－2R水平的变化情况。结果 在可评价的52例（试验组32例,对照组20例）患者中,两组间近期化疗疗效无统计学差异（P＞0．05）。治疗后3、6个月,试验组OKT4／T8比值、NK细胞活性及IL－2水平均较治疗前明显提高（P＜0．05）,但前二项指标与对照组比较无统计学差异（P＞0．05）,而后一项则有明显统计学差异（P＜0．05）;治疗后3、6个月,试验组患者血清SIL－2R水平均较治疗前降低（P＜0．05）,但组间差异比较无统计学意义,而对照组除治疗后6月SIL－2R水平较治疗前明显降低外（P＜0．05）,其余各项指标与治疗前比较均无显著性差异。结论 乌苯美司对肺鳞癌化疗患者OKT4／T8比值、NK细胞活性、血清IL－2和SIL－2R有一定程度的改善作用,但其临床应用价值仍需进一步观察确定。     

免疫营养支持对老年非小细胞肺癌放疗患者营养状况和免疫功能的影响

目的探讨免疫营养支持对老年非小细胞肺癌(NSCLC)放疗患者营养状况和免疫功能的影响。方法选取2013年5月至2015年5月间赤峰学院附属医院红山院区收治的61例老年NSCLC患者为研究对象,采用随机数字表法分为观察组(31例)和对照组(30例)。两组患者均给予放疗、饮食热量供应和抗炎止血治疗,观察组患者在此基础上给予谷氨酰胺和精氨酸治疗,分析两组患者治疗前及治疗后第15天的营养状况和T细胞亚群变化情况。结果治疗后,观察组患者白蛋白(ALB)和前白蛋白(PA)水平均高于对照组,观察组患者CD3+、CD4+及CD4+/CD8+水平均显著升高,CD8+显著降低,对照组患者上述指标呈反向变化,且观察组患者CD3+、CD4+及CD4+/CD8+水平均显著高于对照组患者,CD8+水平显著低于对照组患者,差异均有统计学意义(均P<0.05)。结论老年NSCLC患者放射治疗期间给予免疫营养支持能够显著改善营养状况和T淋巴细胞亚群水平,提高机体免疫功能。     

自体肿瘤疫苗的临床应用研究

目的本文对90例恶性肿瘤患者应用自体瘤苗治疗,探讨自体异构化肿瘤疫苗对细胞免疫功能的影响.方法与对照组比较,通过治疗前后外周血T淋巴细胞亚群CD3,CD4,CD8,CD4/CD8及NK细胞活性检测,观察患者细胞免疫功能的变化情况.结果研究组治疗后CD3,CD4,CD8,CD4/CD8比值和NK细胞的细胞活性都比治疗前显著增加(P＜0.01),而对照组无明显变化(P＞0.05).结论自体肿瘤疫苗有效帮助恶性肿瘤病人重建受损的T淋巴细胞网络,恢复细胞免疫功能,达到治疗和预防肿瘤转移与复发的目的.     

人CD137单抗对急性白血病T淋巴细胞亚群的影响及意义

目的探讨人CD137单抗对急性白血病(acute leukemia,AL)T淋巴细胞亚群的影响,及其在AL免疫治疗中的作用和意义.方法采用免疫荧光标记、流式细胞术(FACS)及体外细胞培养技术,分析人CD137单抗刺激前后22例初治AL患者外周血T淋巴细胞亚群的变化特点.结果人CD137单抗可诱导初治患者外周血T细胞CD3、CD4和CD4/CD8比值显著升高,P＜0.05;从而使其T细胞亚群接近正常,而对于对照组T细胞亚群几无影响.结论人CD137单抗可逆转初治AL患者T细胞缺陷或失衡,使T细胞亚群恢复或接近正常,这对改善患者基础免疫状态,配合联合化疗,具有重要意义;CD137单抗可促使CD4、CD8 T细胞增多,从而参与抗肿瘤免疫反应,可能是AL免疫治疗的重要方法之一,具有一定的临床应用价值.     

The alternation of peripheral lymphocyte subsets in head and neck carcinoma

Peripheral lymphocyte subsets of 115 patients with head and neck carcinomas were examined by the monoclonal antibody technique. In fresh tumor-bearing, the OKT 4 rate was decreased (P less than 0.01) and the OKT 8 rate was increased (P less than 0.05). Consequently the OKT4/OKT8 ratio was decreased (P less than 0.01) compared with normal healthy individuals. This result shows the abnormality of cellular immunity in carcinoma cases. The OKT4/OKT8 ratio reflected the clinical stages and courses sufficiently and correlated with other immunological parameters. The OKT4/OKT8 ratio is considered to be one of the parameters for elucidating the clinical conditions and immunities of carcinoma patients.     

T-Lymphocyte Subsets in Primary Lung Cancer

T-cell subsets in the peripheral blood of 63 primary lung cancerpatients (23 with adenocarcinoma, 23 with squamous cell carcinomaand 17 with small cell carcinoma) and 24 normal healthy controlswere determined by indirect im-munofluorescence, using the monoclonalantibody reagents OKT3, OKT4 and OKT8. Correlations betweenT-lymphocyte subset values and stages or cell types of diseasewere sought. Total lymphocytes in the patient group were decreased.However, no significant difference from controls was seen inthe percentage of OKT3-positive cells (Pan T-cells) in the cancerpatients. The percentage of OKT8-positive cells (cytotoxic/suppressor)was increased in the early stage of disease whereas the percentageof OKT4 positive cells (inducer/helper) remained at the controllevel throughout all stages. The ratio of OKT4-positive to OKT8-positiveT-cells (OKT4/OKT8), reflecting the balance of immunoregula-toryT-cells, was, therefore, significantly decreased in patientswith stage I–II lung cancer (P < 0.05), especiallyin squamous cell lung cancer (P < 0.05), whereas in stagesIII or IV, this T4/T8 ratio returned to the control level. Insmall cell carcinoma, the T4/T8 ratio was significantly decreasedin stage III (P < 0.01) and returned to the control levelin stage IV.     

艾迪注射液防治大肠癌术后早期免疫功能下降的临床疗效

目的 :探讨大肠癌患者手术前后免疫功能的变化 ,以及艾迪注射液防治术后早期免疫功能下降的作用。方法 :大肠癌对照组 30例 ,治疗组 2 0例。每例患者术前及术后 1、2、3周分别采用APAA法测定NK细胞活性和T淋巴细胞亚群。其中治疗组于术前 5d和术后 5d连续使用艾迪 5 0mL +5 %GS4 5 0mL静脉滴入。结果 :大肠癌患者NK细胞活性及OKT3+、OKT4 +明显低于正常组 ,而OKT8+则明显增加 ,P <0 0 5 ,术后免疫功能进一步下降 ,2周后逐渐恢复 ;治疗组术后免疫功能无明显改变。结论 :艾迪注射液对防治大肠癌患者术后早期免疫功能下降 ,具有重要意义     

Suppression of cellular immunity in patients with carcinoma in situ and microinvasive cancer of the cervix uteri]

Monoclonal antibodies (Ortho type) were used for immunocytochemical evaluation of cell-mediated immunity in peripheral blood from 29 patients with in situ (TisNoMo) and microinvasive (T1aNoMo) cervical carcinoma. The total number of T cells (OKT3+) was decreased in both patient groups compared to healthy volunteers. Marked difference between OKT4+ (helper/inducer) and OKT8+ (suppressor/cytotoxic) cells was observed OKT8+ level rose with advancement of disease, resulting in inverted OKT4+/OKT8+ ratio in T1aNoMo cancer patients. Antitumor immune resistance proved inhibited in both study groups manifesting itself in suppression of cell-mediated immunity.     

Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer.

BACKGROUND. The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy using lymphokine-activated killer (LAK) cells generated from tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) was investigated. METHODS. TIL, RLNL, and PBL derived from 39 patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of recombinant interleukin-2. To one group, solid-phase 10 micrograms/ml OKT3 was added during the initial culture period (day 2 or 4). Cytotoxicity against K562 cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of effector cells generated after culturing for 2-3 weeks were studied. RESULTS. Proliferative responses were significantly increased by OKT3 in each type of effector cell (P less than 0.01); in particular, TIL expanded more by OKT3 than PBL and RLNL (P less than 0.01). The population of CD8+ CD11b- cytotoxic T-cells in OKT3-stimulated groups was significantly larger than that in unstimulated groups (P less than 0.01), whereas no differences were observed with CD4+ cells (helper/inducer T-cells) and CD8+ CD11b+ cells (suppressor T-cells). OKT3 enhanced the NK-like activity of TIL and PBL but did not affect their LAK activity. OKT3 suppressed the NK and LAK activity of RLNL. CONCLUSIONS. OKT3 stimulation did not significantly enhance the LAK activity, but the authors propose that OKT3 could be an effective addition to adoptive immunotherapy using TIL due to an increased proliferation and generation of a large cytotoxic T-cell population.     

恶性肿瘤患者T细胞亚群与红细胞免疫功能的变化及其相关性分析

目的：为了提供有意义的免疫治疗,观察恶性肿瘤患者T细胞亚群和红细胞免疫功能变化,并探讨了2系统的相关性。方法采用直接免疫荧光法的流式细胞分析术检测108例恶性肿瘤患者细胞亚群（CD^ 4,CD^ 8_,采用免疫粘附酶母菌花环法检测红细胞免疫功能（C3bRR,ICR)。结果恶性肿瘤患者表现为CD^ 4百分率降低,CD^ 8百分率升高,CD^ 4／CD^ 8比值降低;RBC-C3bRR降低,RBC－ICR升高,以上指标与正常对照组比较均有非常显著性差异,差异（P＜0．01）。各肿瘤组中CD^ 4／CD^ 8与RBC－C3bRR均呈明显正相关（γ=0．65,P＜0．05）。结论恶性肿瘤患者T细胞亚群和红细胞免疫功能变化明显,两者又有明显相关性。     

Monoclonal antibody-defined T-cell phenotypes and phytohemagglutinin reactivity of E-rosette-forming circulating lymphocytes from untreated chronic myelocytic leukemia patients

T-cell phenotypes, as defined by murine monoclonal antibodies, (OKT3, OKT4, OKT8, OKIa1), and phytohemagglutinin (PHA) reactivity, were evaluated in E-rosette forming cells (T-cells) from 10 untreated chronic myelocytic leukemia patients. The proportion of T4+ cells was lower in patients than in controls (41.6 versus 61.7%, P less than 0.02); whereas the proportion of T8+ cells was similar in patients and controls. The decrease in T4+ cells in CML resulted in a decrease in circulating T4+/T8+ ratio (P less than 0.02). The Ia1+ T-cells were increased in most CML (8 of 9) patients, while control subjects never displayed Ia1+ T-lymphocytes (P less than 0.01). The PHA reactivity of E-rosette forming lymphocytes was significantly impaired in CML patients with respect to controls (P less than 0.02). The presence of Ia antigen on T-cells was positively correlated with the T8+ cell phenotype (P less than 0.001) and inversely correlated with the T4+ (helper) cell phenotype (P less than 0.05). Furthermore, there was a trend towards an inverse correlation between the PHA response and the level of Ia1+ or T8+ cells, there is no correlation between PHA reactivity and T4+ phenotype. The results suggest that the T-lymphocyte population from untreated CML patients is intrinsically abnormal.     

肾癌术后免疫治疗T细胞亚群检测及疗效观察

目的:检测肾癌术后患者IL-2免疫治疗前后对外周血T淋巴细胞亚群的水平影响,进一步观察其对肾癌术后患者的疗效。方法:肾癌术后患者98例随机分为两组:实验组58例采用IL-2治疗,皮下注射小剂量（60-100万IU/次）,隔日1次,共3月,以后每年方案同前1年。对照组40例只给予肾癌根治术,不予免疫治疗。应用流式细胞技术检测两组患者不同时间段（治疗前,治疗后2月、6月）外周血CD3+、CD4+、CD8+、CD4+/CD8+,并进行对比研究。观察两组治疗后1年、3年生存率、生活质量(KPS)评分以及不良反应。结果:实验组与对照组CD3+、CD4+、CD4+/CD8+在治疗前无明显差异(P＞0.05),治疗后2月、6月较对照组明显升高(P＜0.05)。术后1年实验组生存率100％(58/58),对照组97.5%（39/40）,两者无明显差异(P＞0.05);术后3年实验组生存率84.5％（49/58）,明显高于对照组（67.5%,27/40)(P＜0.05)。实验组术后1年生活质量评分平均升高19.6分,3年生活质量评分平均升高11.5分,均明显高于对照组3.7分、1.4分(P＜0.05)。实验组不良反应共12例,均为一过性,未影响免疫治疗。对照组无相关不良反应。结论:肾癌根治术后应用IL-2进行免疫治疗,可以提高患者免疫水平,发挥抗肿瘤作用,提高生存率,改善生活质量,不良反应较轻。     

TCGA database analysis of the tumor mutation burden and its clinical significance in colon cancer

BackgroundColon cancer is one of the most common malignant tumors, with high rates of incidence and death. The tumor mutational burden (TMB), which is characterized by microsatellite instability, has been becoming a powerful predictor which can show tumor behavior and response to immunotherapy.MethodsIn this study, we analyzed 437 mutation data of colon cancer samples obtained from The Cancer Genome Atlas (TCGA) and divided patients into low- and high-TMB groups according to the TMB value. Then we identified differentially-expressed genes (DEGs), conducted immune cell infiltration and survival analyses between groups.ResultsThe higher TMB of the patients with colon cancer predicts a poorer prognosis. Functional analysis was performed to assess the prognostic value of the top 30 core genes. The CIBER-SORT algorithm was used to investigate the correlation between the immune cells and TMB subtypes. An immune prognosis model was constructed to screen out immune genes related to prognosis, and the tumor immunity assessment resource (TIMER) was then used to determine the correlation between gene expression and the abundance of tumor-infiltrating immune cell subsets in colon cancer. We observed that APC, TP53, TTN, KRAS, MUC16, SYNE1, PIK3CA have higher somatic mutations. DEGs enrichment analysis showed that they are involved in the regulation of neuroactive ligand-receptor interaction, the Cyclic adenosine monophosphate (cAMP) signaling pathway, the calcium signaling pathway, and pantothenate and Coenzyme A (CoA) biosynthesis. The difference in the abundance of various white blood cell subtypes showed that Cluster of Differentiation 8 (CD8) T cells (P=0.008), activated CD4 memory T cells (P=0.019), M1 macrophages (P=0.002), follicular helper T cells (P=0.034), activated Natural killer (NK cell) cells (P=0.017) increased remarkably, while M0 macrophages significantly reduced (P=0.025). The two immune model genes showed that secretin (SCT) was negatively correlated with survival, while Guanylate cyclase activator 2A (GUCA2A) was positively correlated.ConclusionsThis study conducted a systematically comprehensive analysis of the prediction and clinical significance of TMB in colon cancer in identification, monitoring, and prognosis of colon cancer, and providing reference information for immunotherapy.