肺鳞癌TIL的体外扩增、抗瘤活性及表型分析

本文对8例人原发性肺鳞癌的TIL进行分离培养并检测了TIL的抗瘤活性及细胞表型。结果表明8例TIL的平均扩增倍数为430；TIL在10．30天之间显示出高水平的非特异性杀伤活性，10-20天时对A1及Daudi的杀伤百分率分别为79．2％和43．4％，20．30天时分别为51．7%和27．9%。非特异杀伤活性在30天以后降至较低水平。     

肿瘤浸润淋巴细胞的表型及功能研究

肿瘤浸润淋巴细胞的表型及功能研究江青综述林芷英审校上海中山医院肝癌研究所（２０００３２）肿瘤浸润淋巴细胞（ｔｕｍｏｒ－ｉｎｆｉｌｔｒａｔｉｎｇｌｙｍｐｈｏｃｙｔｅ，ＴＩＬ）具有杀伤肿瘤细胞、降低转移潜能的作用，因其与肿瘤细胞密切接触而被认为是宿主对肿...     

卵巢癌浸润淋巴细胞的免疫学特性研究

目的 研究卵巢癌浸润淋巴细胞（ＴＩＬ）在体外扩增后免疫学特性,评估ＴＩＬ用于晚期卵巢癌治疗的前景。方法 利用流式细胞仪分析ＴＩＬ的细胞表型,使用分子生物学和免疫学方法研究ＴＩＬ分泌细胞因子的能力和杀伤肿瘤细胞的活性。结果 ＴＩＬ细胞表型的差异可能与肿瘤的种类,性质,取材部位有关,结缔组织,基质中来源的ＴＩＬ以ＣＤ＾＋３,ＣＤ＾＋４为主,肿瘤组织和小血管周围以ＣＤ＾＋３,ＣＤ＾＋８为主,体外ＩＬ－２     

肿瘤浸润淋巴细胞的原位特征及其临床应用

肿瘤浸润淋巴细胞的原位特征及其临床应用陈一鸣综述尤胜国郝玉书杨天楹审校中国医学科学院血液学研究所血液病医院（天津市３０００２０）７０年代，人们发现许多人类实体瘤被大量单个核细胞（ＭＮＣ）浸润或包围，这些浸润的ＭＮＣ对肿瘤生长和转移以及对肿瘤患者生存期...     

肝细胞性肝癌组织浸润淋巴细胞表型与分布研究

目的:肝细胞性肝癌组织浸润淋巴细胞与外周血T 细胞表型可能与肿瘤进展及预后相关,本研究检测肝癌患者组织及外周血T 细胞表型与分布,分析淋巴细胞表型变化与预后的关系。方法:分析2007年10月至12月中山医院147 例肝癌及癌旁组织浸润淋巴细胞表型（T 细胞或B 细胞表面标志物:CD3、CD8、CD4、CD20、CD19、Foxp 3）,表型与临床病理特征及预后的关系;检测26例肝癌外周血CD3、CD8、CD4 +T细胞数量并其比例变化。结果:癌巢内肿瘤浸润细胞明显少于癌周组织（P < 0.01）,癌周淋巴细胞主要分布于癌旁正常肝组织、汇管区,其与患者肝炎病史及肝硬化相关,表型以CD3 +T细胞为主,其中又以CD8 + 细胞毒性T 细胞为主;CD4 染色在多数病例为阴性,Foxp 3 仅在个别病例（15/ 109）呈阳性。肿瘤浸润淋巴细胞B 细胞标志CD20、CD19均为阴性。肿瘤组织内CD8 +T细胞浸润数量与预后正相关,而癌周浸润淋巴细胞数目与患者转移及复发无显著关系。结论:肝癌肿瘤浸润细胞在癌巢内明显少于癌周组织,肿瘤及癌周浸润细胞以CD8 + 细胞毒性T 细胞为主。肿瘤组织内CD8 +T细胞浸润数量与预后相关,而癌周浸润淋巴细胞数量与患者转移及复发无显著关系。      

肝癌肿瘤浸润淋巴细胞抗瘤活性及表型特征

目的 探讨肝癌肿瘤浸润淋巴细胞的抗瘤活性及表型特征。方法 13例肝癌患者(7例接受术前TACE，6例未接受)，MTT法检测TIL细胞抗肿瘤活性，APAAP法检测TIL细胞表型。结果 TACE组TIL细胞在第2周增殖达到高峰，至第3周平均扩增52倍，而未接受术前化疗组在第3周扩增达到高峰，平均扩增了12倍。术前介入化疗患者TIL细胞肿瘤杀伤活性增强，CD3^ 、CD4^ 、CD8^ 不同程度的增加。结论 术前介入化疗可缩短肝癌患者TIL细胞增殖时间，提高肿瘤杀伤活性。     

人肿瘤浸润淋巴细胞（TIL）的抗肿瘤活性及与外周血淋巴细胞...

In order to search for more efficient effector cells than the classical LAK cells for tumor immunotherapy, antitumor activity of TIL was studied. Although fresh TIL were unable to kill both NK-sensitive K562 and NK-resistant Anip 973 targets, rIL-2 activated TIL from 8 lung carcinoma and 4 gastric cancer patients did express significant cytotoxicity against allogeneic solid tumor targets Antitumor activity of activated TIL was more efficient than that of activated autologous PBL By limiting dilution assay, TIL were shown to have a higher frequency of LAK precursors than PBL.     

高海拔地区慢性淋巴细胞白血病免疫表型特征分析

目的:分析高海拔地区慢性淋巴细胞白血病(chronic lymphoid leukemia,CLL)免疫表型特点。方法:采用CD45/SSC双参数设门,应用三色流式细胞术对高原地区26例CLL患者进行免疫分型。结果:26例患者中CD5、CD19、CD22、CD20、CD23、HLA-DR、CD11c、CD10、κ轻链、λ轻链的阳性率分别是96.2%、92.3%、96.2%、96.2%、88.5%、92.3%、57.7%、15.4%、100%、100%,而CD34、CD38、FMC7以及T细胞相关抗原CD3、CD4、CD8检测呈阴性。结论:与典型的CLL免疫表型特征相比,CD22高阳性率,CD11c和CD10的伴随表达,以及κ轻链和λ轻链同时双阳性表达有可能是高海拔地区CLL的重要免疫表型特征。本研究可为高海拔地区CLL免疫表型分析提供参考和鉴别诊断依据。     

肿瘤浸润淋巴细胞免疫治疗胃癌的疗效研究

对部分胃癌患者进行肿瘤浸润淋巴细胞（ＴＩＬ）免疫治疗。临床研究显示，ＴＩＬ免疫治疗可使胃癌患者瘤体部分缩小，存活期延长，临床一般症状明显改善。通过ＯＫＴ比值、ＳＩＬ２Ｒ、ＮＫｃ等免疫指标观察，发现ＴＩＬ治疗胃癌患者可以体免疫功能，促进其抗癌消瘤的能力。作者认为，对于胃癌患者的综合治疗而言，ＴＩＬ免疫治疗是主要方法之一，它可以调节机体免疫功能的平衡，减轻病员痛苦，改善临床症状，延长其存活期。     

树突细胞对肿瘤浸润淋巴细胞抗乳腺癌免疫活性影响的研究

背景与目的:树突细胞(dendriticcell,DC)又称树突状细胞,是目前已知的功能最强的抗原呈递细胞,它可以在体内、外向T淋巴细胞呈递抗原,并诱发细胞毒T淋巴细胞(cytotoxicTlymphocyte,CTL)反应。本研究旨在探讨DC激活的肿瘤浸润淋巴细胞(tumorinfiltratinglymphocytes,TIL)体外对乳腺癌细胞的杀伤活性。方法:从乳腺癌患者外周血获取DC,应用粒/巨噬细胞集落刺激因子(granulocyte/macrophagecolonystimulatingfactor,GM-CSF)、白细胞介素-4(interleukin-4,IL-4)和肿瘤抗原激活DC,然后用DC激活TIL,观察TIL在体外对自体乳腺癌细胞和Bcap-37乳腺癌细胞的杀伤活性。结果:DC激活的TIL对自体乳腺癌细胞具有很强的杀伤活性,杀伤率为(85.76±2.93)%,明显高于未经DC激活的TIL、DC激活的T淋巴细胞和未经DC激活的T淋巴细胞对自体乳腺癌细胞的杀伤率犤分别为(52.11±1.48)%、(51.35±1.46)%和(3.59±0.25)%犦。而它们对Bcap-37乳腺癌细胞的杀伤活性则相对较低犤分别为(40.03±1.29)%、(22.09±0.87)%、(21.66±0.85)%和(1.76±0.14)%犦。结论:乳腺癌患者外周血DC能诱导TIL产生高效而特异的抗乳腺癌免疫活性。     

BCG及IL-2激活膀胱癌患者PBMC及TIL细胞的抗癌活性比较

 用Whitesides法从15例膀胱移行细胞癌患者外周血及癌手术标本中获得的外周血单个核细胞（PBMC）及肿瘤浸润淋巴细胞（TIL）,分别用活BCG、死BCG及IL－2刺激培养,计算细胞增殖倍数并测定其抗癌活性。结果,死BCG对细胞并无激活作用;IL－2对细胞的诱导增殖作用强于活BCG,而其激活这两种细胞的抗癌活性低于活BCG激活的抗癌活性。BCG对免疫受抑制的PBMC及YIL细胞的激活作用可能是BCG抗肿瘤重要作用机理之一。并为BCG的进一步临床免疫治疗奠定理论基础。     

Adjuvant, adoptive immunotherapy with tumor infiltrating lymphocytes plus interleukin-2 after radical hepatic resection for colorectal liver metastases: 5-year analysis

BACKGROUND AND OBJECTIVES: Conventional chemotherapy has not proven effective in improving long-term results of surgery for liver metastases from colorectal cancer. We assessed the usefulness of immunotherapy with tumor infiltrating lymphocytes (TIL) plus Interleukin-2 (IL-2) as adjuvant treatment. METHODS: Between 1995 and 1998, 47 patients were enrolled onto a prospective protocol; 25 entered the treatment group (A) and 22 entered the control group (B). All patients had undergone radical liver resection. TIL obtained from surgical specimens from group A patients were cultured and activated in vitro with IL-2, then reinfused into the patients with IL-2. We investigated pre- and post-IL-2 stimulation expression of T cell receptor (TCR) zeta- and epsilon-chains, p56(lck), Fas, and Fas-L by TIL immunostaining. RESULTS: Fourteen patients from group A (56%) received immunotherapy; 14 from group B (60%) underwent conventional chemotherapy, and the remaining 19 patients did not receive any treatment. No significant differences between the two groups were found in the actuarial and disease-free survival (DSF) rates after 1, 3, and 5 years. After IL-2 exposure, TCR zeta-chain expression significantly increased (P = 0.001); An increase in TCR epsilon-chain expression (P = 0.04), and p56(lck) (P = 0.03) was detected; TCR epsilon-chain expression was significantly increased in disease-free patients compared to those who relapsed (P = 0.04). Fas-L expression was correlated with the TCR epsilon-chain and p56(lck) levels (P = 0.05). CONCLUSIONS: Our data suggest that we are still a long way from being able to propose TIL + IL-2 treatment as an effective adjuvant therapy. However, the results confirm that the biological indicators examined could play an important role in modulating immunitary response against tumor cells.     

The expression and clinical value of tumor infiltrating dendritic cells in tumor tissues of patients with esophageal cancer

BackgroundAs dendritic cells (DCs) are the major antigen-presenting cells of the immune system, understanding their role in esophageal cancer is essential for the development of preventative and treatment strategies. This study investigated the expression level and clinical value of tumor infiltrating dendritic cells (TIDCs) in tumor tissues of patients with esophageal cancer.MethodsFrom January 2019 to January 2021, 184 patients with esophageal cancer treated were prospectively enrolled as the observation group and 184 patients with benign esophageal tumors were selected as the control group. Tumor tissue samples were obtained and the expression level and phenotypes of the TIDCs were analyzed. The correlation between TIDC expression and clinical characteristics of patients with esophageal cancer was investigated.ResultsThe density of the TIDCs in the observation group was lower than that in the control group (8.76±2.25 vs. 9.97±2.19; P=0.000). Furthermore, the percentage of major histocompatibility complex-II (MHC-II) positive DCs and the percentage of CD54 positive DCs were relatively lower in the observation group compared to the control group (6.60%±2.12% vs. 9.34%±2.41%; P=0.000 and 7.41%±2.36% vs. 9.98%±2.47%; P=0.000, respectively). Esophageal cancer patients with lymph node metastasis had lower TIDC density, lower percentage of MHC-II positive DCs, and lower percentage of CD54 positive DCs compared to patients without node metastasis (P<0.05). Patients with stage III esophageal cancer also showed significantly lower TIDC density, lower percentage of MHC-II positive DCs, and lower percentage of CD54 positive DCs compared to patients with stage I/II esophageal cancer (P<0.05). Esophageal cancer patients with tumor diameter ≥4 cm presented with decreased TIDC density, decreased percentage of MHC-II positive DCs, and decreased percentage of CD54 positive DCs compared to patients with tumor diameter <4 cm (P<0.05). In addition, the density of TIDCs, the percentage of MHC-II positive DCs, and the percentage of CD54 positive DCs were significantly negatively correlated with the percentage of CD4⁺ T-lymphocytes and positively correlated with the percentage of CD8⁺ T-lymphocytes (P<0.05).ConclusionsPatients with esophageal cancer had low expression and function of TIDCs, and this was related to the imbalance of T-lymphocyte subsets, lymph node metastasis, TNM stage, and lesion size.     

TIL细胞治疗恶性胸水的疗效观察

目的观察肿瘤浸润淋巴细胞(TIL)治疗恶性胸水的疗效。方法从30例恶性肿瘤胸水中的肿瘤细胞分离得到TIL,并经10%人AB血清RPM I-1640液培养,经rIL-2体外激活培养,随后胸腔注射。结果完全缓解12例(40.0%),有效15例(50.0%),无效3例(10.0%),总有效率90.0%(27/30)。结论 TIL治疗恶性胸腔积液疗效好,毒副作用小,能改善患者的生活质量。     

肺癌TIL抗瘤活性、表型分析及临床应用的初步观察

目的 从肺癌患者手术切除的肿瘤组织中分离出肿瘤浸润淋巴细胞（TIL）,经rIL-2体外激活培养,研究TIL对瘤细胞的杀伤活性及其表型变化,并对其回输后的毒副反应及患者免疫功能 变化进行了观察。方法 从51例肺癌患者手术切除的实体瘤中分离得到TIL,并经10％人AB血清RPMI－1640液培养。12例在培养前、后应用3H－TdR释放实验测定TIL对自体瘤细胞和801－D细胞的杀伤作用,13例用间接免疫荧光法测定了淋巴细胞表型CD3^ 、CD4^ 、CD8^ 比例的变化。15例患者静脉输注了活化的自体TIL。结果 TIL在培养第25天左右对自体瘤细胞和801－D细胞的杀伤力比培养当天有显著性提高;淋巴细胞表型分析示CD3^ 、CD8^ 比例在培养过程中有明显提高,而CD4^ 比例和CD4^ /CD8^ 比例变化不大;自体回输的15例患者一般状况好, 无明显毒副反应,辅助检查无异常改变,免疫功能增强,复查血尿常规、生化、心肺功能等均无异常改变,远期疗效正在观察中。结论 大部分病例短期即可回输TIL,且毒副反应小,因此肺癌TIIL过继免疫治疗是一种值得在临床进一步研究的免疫治疗方法。     

拉司太特单药治疗晚期恶性晚期20例报告

目的　评价拉司太特胶囊单药的临床疗效并观察临床应用中的毒副作用。方法　采用拉司太特单药治疗晚期恶性肿瘤 2 3例 ,可评价 2 0例。结果　总有效率 3 5 .0 0 % ,对小细胞肺癌为 5 5 .60 % ( 5 /9) ,对非小细胞肺癌为 16.67%( 1/6) ,对胃癌为 2 5 % ( 1/4)。剂量限制毒性为骨髓抑制 ,有轻度消化道反应 ,对肝肾功能无明显影响。结论　拉司太特单药治疗晚期肿瘤有一定疗效 ,毒副反应可以耐受。     

Prognostic and predictive value of tumor infiltrating lymphocytes in early breast cancer

It is well recognized that the immune system plays an essential role in tumor defense. The presence of tumor-infiltrating lymphocytes reflects an individual immunological response. In early breast cancer, the presence of TILs is associated with a more favorable outcome and response to therapy. In this review, we describe how TILs are assessed. Also, we discuss their role as prognostic and predictive biomarker in the neoadjuvant and adjuvant settings as well as in residual disease. Moreover, we discuss the possible implementation of TILs in daily clinical practice as well as in future clinical trials in order to fine tune prognosis and improve treatments.     

Analysis of telomere damage by fluorescence in situ hybridisation on micronuclei in lymphocytes of breast carcinoma patients after radiotherapy

Radiotherapy has become an indispensable tool in the effective management of most of the cancers. There have been efforts earlier to study the differential radio-sensitivity patterns in patients undergoing radiation treatment to correlate with treatment induced complications such as tissue injury, cell death, and chromosomal aberration frequencies etc. The present study is an attempt to correlate the radiation-induced damage in the peripheral blood lymphocytes (PBLs) of breast cancer patients with the frequency of telomere mediated chromosomal damage. Blood samples from 55 patients with (Gr-II and Gr-III) CA-breast were obtained pre- and post-radiotherapy. The patients were treated with external beam radiotherapy of 50.4 Gy over a period of 6 weeks. Chromosome damage was measured by analysing micronucleus (MN) frequency in PBLs. The MN-frequency of the irradiated patients increased significantly compared to the patients being self-controls. The micronuclei were hybridized with telomere probes to study the extent of telomere damage. The fluorescence signals of the telomere regions in the first generation of the binucleated cells were significantly higher in the post-radiotherapy patients. There was also significant correlation observed in the patients with higher-grade tumours. Inter-individual variability was observed in the radiation-induced MN frequency in lymphocytes of patients after six weeks of radiotherapy. There was a significant correlation between functionally intact telomeres and the cellular response to ionising radiation. Our findings suggest that fluorescence in situ hybridisation on micronuclei could be effectively used as routine clinical application to determine the individual sensitivity to ionising radiation with respect to telomere damage.