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肿瘤浸润淋巴细胞及重组白细胞介素2治疗原发性肝细胞癌 总被引:1,自引:1,他引:0
目的探讨联合应用肿瘤浸润性淋巴细胞(tumorinfitratinglymphocytes,TIL)和重组白细胞介素2(rIL2)治疗对原发性肝细胞癌(primaryhepatocelularcarcinoma,PHCC)术后患者细胞免疫功能的影响和其临床疗效。方法对16例PHCC术后患者进行了TIL和rIL2治疗,12例从肝动脉插管输入,4例从门静脉插管输入。结果TIL治疗后16例患者外周血白细胞介素2(IL2),T细胞亚群及比率均有不同程度上升;肿瘤坏死因子(TNF),白细胞介素6(IL6)多有不同程度下降。随访6~24个月,14例肝癌根治性切除术患者,肿瘤无复发迹象,1例肝癌根治切除术患者TNF上升了8IU,该患者治疗8个月后死于肝功能衰竭;1例肝癌姑息性切除,残癌无水酒精注射病人,TIL治疗18个月后肿瘤直径扩大2cm。结论TIL治疗对提高PHCC术后患者抗肿瘤细胞免疫功能,防止肿瘤复发,抑制残瘤生长,延长患者生存期具有一定作用。 相似文献
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肿瘤浸润淋巴细胞、重组白细胞介素2治疗对手术后原发性肝癌病人细胞免疫功能的影响 总被引:3,自引:1,他引:2
对5例经手术切除的原发性肝癌病人用肿瘤浸润淋巴细胞(TIL)和重组白细胞介素2(rIL-2)治疗。治疗前1周及治疗后1个月检测细胞免疫功能,治疗后外周血淋巴细胞的NK活性、白细胞介素2产生及活性均明显升高;植物血凝素(PHA)皮试阴性转阳性。提示;rIL-2和TIL应用可明显提高原发性肝癌病人的细胞免疫功能,对杀灭残留癌细胞,抗肿瘤复发、转移,提高远期疗效有一定作用。可能成为肝癌术后抗肿瘤复发,转移的重要疗法。 相似文献
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可溶性白细胞介素2受体(sIL—2R)与大肠癌 总被引:2,自引:0,他引:2
雷雯 《国外医学(外科学分册)》1997,24(6):322-323
恶性肿瘤血清可溶性白细胞介素2受体(sIL-2R)水平增高是肿瘤诱导的免疫反应所致。大肠癌血清sIL-2R水平明显比正常人群高,且与大肠癌临床分期有关,根治性大肠癌切除术后2周sIL-2R可降至正常水平,研究表明sIL-2R水平与大肠癌患者的免疫状态及病情严重程度有关。 相似文献
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对25例恶性肿瘤患者单独或配合化疗使用重组人白细胞介素-2(rIL-2)的疗效进行临床观察。25例中男性15例,女性10例。平均年龄53.1岁。肺癌7例,乳腺癌5例,结肠癌4例,直肠癌3例,肝癌、胃癌各2例,肾癌、神经纤维肉瘤各1例,分别采用全身静脉、瘤内注射、体腔内注射、介入动脉灌注等途径给药。观察结果:完全缓解2例,部分缓解6例,稳定20例,总有效率为28.6%。表明rIL-2对改善恶性肿瘤患者的生活质量有一定帮助与化疗配合能提高疗效,且毒副反应轻。 相似文献
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白细胞介素(IL)-2与IL-4对小鼠膀胱癌肿瘤浸润性淋巴细胞增殖及细胞毒性的协同调节作用 总被引:4,自引:1,他引:3
目的 探讨白细胞介素(IL)-2与IL-4对膀胱癌肿瘤浸润性淋巴细胞(TIL)体外增殖及细胞毒性免疫调控的协同作用。方法 分离膀胱癌TIL,置于含IL-2和(或)IL-2的完全培养基因中培养4周,定期计数TIL增殖数量。四甲基偶氮唑蓝(MTT)比色法检测TIL细胞毒性。结果 对比单纯IL-2的培养条件,IL-2联合IL-4后4周时TIL扩增数量是前者的1.65倍(P〈0.05)。在交靶比为10:1时,TIL对自体膀胱癌细胞(BTT739)表现出高水平的杀伤活性(P〈0.05)。联合培养的TIL抗BTT39或小鼠淋巴瘤瘤株(YAC-1)的活性与在单纯IL-2培养的条件下相比无显著改变(P均〉0.05)。结论 IL-4对IL-2活化的膀胱癌TIL增殖具有较强的正向调节效应,而对TIL细胞毒性未见明显影响。 相似文献
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恶性肿瘤血清可溶性白细胞介素2受体(SIL-2R)水平增高是由肿瘤诱导的免疫反应所致。大肠癌血清SIL-2R水平明显比正常人群高,且与大肠癌临床分期有关,根治性大肠癌切除术后2周SIL-2R可降至正常水平。研究表明sIL-2R水平与大肠癌患者的免疫状态及病情严重程度有关。 相似文献
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对3例膀胱移行细胞病患者手术切除的肿瘤组织中肿瘤浸浸润性淋巴细胞进行了体外分离与培养,结果2例获得成功,TIL体外扩增培数分别达58-170,在培养24d时对自体肿瘤靶细胞的最高杀伤活性达41%以上,且呈现一定的靶细胞特异性。 相似文献
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目的:了解原发性肝癌患者肿瘤浸润T淋巴细胞中CD4+及CD8+的表达特点。方法:收集30例原发性肝癌患者(均有乙型肝炎病毒感染背景)的癌组织(乙肝肝癌组)和癌旁组织(乙肝癌旁组)以及30例因良性病变而行肝切除的患者的新鲜肝组织(对照组),分离组织浸润淋巴细胞,用抗CD3、CD4和CD8单克隆抗体同时荧光染色,用流式细胞仪检测各表面标志的表达情况。结果:1)乙肝肝癌组、乙肝癌旁组及对照组CD3+CD4+T细胞占浸润淋巴细胞的比例分别为(22.31±3.68)%、(10.69±2.47)%及(4.21±4.26)%。乙肝肝癌组显著高于乙肝癌旁组及对照组,差异有统计学意义(P=0.000,P=0.001),乙肝癌旁组高于对照组,差异亦有统计学意义(P=0.019)。2)乙肝肝癌组、乙肝癌旁组及对照组CD3+CD8+T细胞占浸润淋巴细胞的比例分别为(26.10±5.82)%、(21.82±2.70)%及(41.31±14.01)%,乙肝肝癌组及乙肝癌旁组显著低于对照组,差异有统计学意义(P=0.014,P=0.004),而乙肝肝癌组与乙肝癌旁组之间差异无统计学意义(P=0.651)。3)乙肝肝癌组组织浸润淋巴细胞中CD3+CD4+T细胞与CD3+CD8+T细胞的比值为0.91±0.30,显著高于乙肝癌旁组(0.47±0.11,P=0.003)及对照组(0.11±0.13,P=0.000),CD3+CD4+与CD3+CD8+T细胞的比值出现失衡。结论:原发性肝癌患者肿瘤浸润淋巴细胞中T细胞亚群失调,表现为CD3+CD4+T细胞所占比例升高,CD3+CD8+T细胞所占的比例下降,CD3+CD4+/CD3+CD8+明显升高。 相似文献
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目的:研究肾细胞癌组织中肿瘤浸润淋巴细胞(TIL)的分布特点及其与预后的关系.方法:对52例肾透明细胞癌组织T,辅助T及自然杀伤细胞(NK细胞)进行原位免疫组化研究,并与病人预后作相关性分析.结果:TIL细胞中主要为T细胞,占70%;TIL细胞表达的程度对肾细胞癌患者预后的影响较大(P<0.01);TIL细胞亚群之间的表达为正相关.结论:TIL在对抗肾细胞癌中起较重要的作用,它们的表达程度影响预后. 相似文献
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BackgroundPregnancy-associated breast cancer (PABC) refers to breast cancers (BC) diagnosed during pregnancy or shortly after birth. Although the inflammatory environment of post-partum PABC cases (designed as PP-PABC) may be deleterious, so far PP-PABC have scarcely been distinguished from breast cancers diagnosed during pregnancy. Furthermore, whether PP-PABC cases have an enhanced immune infiltration remains unknown. We investigated chemosensitivity, immune infiltration and survival of PP-PABC patients treated by neoadjuvant chemotherapy (NAC) compared to non-PABC matched BC patients.Materials and methodsWe identified PP-PABC cases among a cohort of 1199 invasive BC treated with NAC between 2002 and 2012. Each PP-PABC case was matched with 3 non-PABC controls, according to age and pathological breast cancer subtype. Microbiopsy specimens and paired surgical samples were evaluated for stromal lymphocyte infiltration. Association of clinical and pathological factors with pathological complete response (pCR) and disease-free survival (DFS) was assessed by univariate and multivariate analyses.ResultsOur final population study was composed of 116 patients (29 PP-PABC and 87 non-PABC). Median follow-up was of 49.0 and 29.3 months, respectively. After NAC, pCR rates (p = 0.64), post-NAC immune infiltration (stromal TILs: p = 0.67; intratumoral TILs: p = 0.14), and DFS rates (p = 0.17) were comparable between PP-PABC and non-PABC patients in global population. Similar results were found after stratification by pathological subtype.ConclusionWe observed similar patterns between postpartum PABC and control tumors in terms of chemosensitivity, immune infiltration, and prognostic. Our results enhance the idea that PP-PABC should receive the same standard of care treatment as other patients, including neoadjuvant chemotherapy. 相似文献
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BackgroundHigh levels of tumor-infiltrating lymphocytes (TILs) in primary triple negative and HER2-positive breast cancer (BC) have been associated with an improved patients' outcome. The role of TILs in Luminal (hormone receptor positive and HER2 negative) tumors remains to be elucidated. Moreover, the association between TILs and prognosis in the metastatic setting is still unknown.Patients and methodsWe evaluated the relationship between TILs and time to progression (TTP) in metastatic BC patients enrolled in a prospective phase II trial of metronomic chemotherapy, that used cyclophosphamide 50 mg daily, capecitabine 500 mg thrice daily and vinorelbine 40 mg orally three times a week (VEX combination).ResultsOf the 108 ER + BC patients enrolled in the VEX trial, 92 (85%) had sufficient tumor tissue and were assessed for TILs in H&E stained slides. TILs were evaluated in 38 primary BC samples and 54 metastatic sites. High (≥10%) TILs levels were significantly correlated with high Ki-67 labeling index. At multivariable analysis, each 10% increase in TILs strongly predicted a worse TTP (HR: 1.27, p = 0.008). VEX trial patients, categorized by a 3 tiers system (0–4%, 5–9% and >10% TILs) showed significantly different progression free survival curves (p = 0.011).ConclusionsHigh TILs levels are significantly associated with a worse TTP in Luminal metastatic BC patients treated by metronomic chemotherapy. Our data confirm the reliability of TILs as a biomarker in the BC metastatic setting. The putative unfavorable prognostic role of TILs in Luminal BC patients might have clinical utility if validated by further studies. 相似文献
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Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma
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Nghia Nguyen MD Emily Bellile MS Daffyd Thomas MD Jonathan McHugh MD Laura Rozek PhD Shama Virani PhD Lisa Peterson MPH Thomas E. Carey PhD Heather Walline PhD Jeffery Moyer MD Matthew Spector MD Daniel Perim BS Mark Prince MD Scott McLean MD Carol R. Bradford MD Jeremy M. G. Taylor PhD Gregory T. Wolf MD Head Neck SPORE Program Investigators 《Head & neck》2016,38(7):1074-1084
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P. Ditonno C. L. Tso T. Sakata J. B. de Kernion A. Belldegrun 《Urological research》1992,20(3):205-210
Summary Biological therapy using a combination of lymphokine and tumor infiltrating lymphocytes (TILs) is a new approach to the treatment of patients with advanced cancer. To improve the potency of TILs, new cytokines with T-cell stimulatory effects used alone or in combination with interleukin-2 (IL-2) are currently being investigated. We have studied the effect of interleukin-7 (IL-7) on TILs derived from renal cell carcinoma. Our data demonstrated that five of ten TILs proliferated in response to IL-7 alone. This proliferative response was 73–90% less than that obtained with IL-2 alone. The use of IL-7 plus IL-2 resulted in a 1.2- to 4.7-fold increase in proliferation of six of ten TILs compared with IL-2 alone. IL-7-driven TIL growth was consistently blocked by anti-IL-2, anti-IL-2R and anti-IL-7 antibodies (37.2%, 41.6% and 82.2% suppression, respectively). The expression of IL-2 receptors was also significantly increased in the presence of IL-7 or IL-7 phytohemagglutinin (40.6+3.8 and 72.5+1.5). In comparison with IL-2, IL-7 treatment was associated with a decrease in CD56 (46.3%±19 vs 10%±4.9) and increase in CD3 (29.3%±12 vs 73%±6.4) and CD 4 (19.3%±15 vs 58%±10). These studies suggest that in some renal TILs, IL-7 and IL-2 can have a synergistic proliferative effect. The IL-7 stimulatory effect appears to be mediated via both an IL-2 pathway and an IL-7-independent pathway.This paper was selected for publication in Urological Research from the program of the 1991 meeting of the European Society of Urological Oncology and Endocrinology (ESUOE) 相似文献
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目的 探讨肿瘤浸润性淋巴细胞(TIL)对原发性肝癌(HCC)患者术后细胞免疫功能的影响和临床疗效及半乳糖抗CD3单克隆体-TIL复合物(Gal-Anti-CD3-McAb-TIL)体外及体内的趋肝性。方法 (1)对30例HCC患者术后进行了TIL和重组白介素-2(rIL-2)治疗。(2)制备半乳糖基抗CD3单克隆抗体-TIL(McAb-TIL)复合物。将TIL和McAb-TIL分别与小鼠肝细胞置CO2孵箱中孵育,用倒置相差显微镜观察其趋肝性。将^125I-TIL和^125I-McAb-TIL分别经小鼠尾静脉注入,观察示踪剂在脏器中的分布。结果 TIL治疗后,30例患者外周rIL-2、T细胞亚群均有上升。24例肝癌根治性切除术患者随访60-48个月无复发。McAb-TIL与细胞有明显粘附,给小鼠静脉注射后,TIL和McAb-TIL主要在肺中积聚,在肝内浓度较低。结论 TIL治疗可能提高HCC患者术后抗钟瘤细胞免疫功能。TIL与半乳糖抗CD3单克隆抗体结合物体内肝靶向性不明显。 相似文献
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Kapoor S Pal S Sahni P Dattagupta S Kanti Chattopadhyay T 《The Journal of surgical research》2005,129(2):172-175
BACKGROUND: Pilot studies have shown that histamine H2 receptor antagonists augment the natural immunity against cancer in colorectal and gastric cancer by enhancing lymphocytic infiltration in the tumors. However, a study of adjuvant ranitidine failed to show a significant benefit in colorectal cancer, possibly because of the immunosuppression exerted by blood transfusion and post-operative infections. The pre-operative use of H2 receptor antagonists may therefore be of greater benefit. Except for a pilot study using cimetidine, there are no trials that have evaluated the effect of pre-operative H2 receptor antagonists on tumor infiltrating lymphocytes in colorectal cancer. OBJECTIVE: To evaluate the efficacy of famotidine in augmenting tumor infiltrating lymphocytes in colorectal cancer. STUDY DESIGN: Double blind, placebo controlled, prospective randomized study. METHODS: Twenty-three patients with resectable colorectal cancer were randomized to receive famotidine (n = 11) or placebo (n = 12). Famotidine was given for 1 week pre-operatively in a dose of 40 mg per day p.o. After resection, the specimens were analyzed histologically for lymphocytic infiltration by a pathologist blinded to the two groups. Lymphocytic infiltration more than 50 cells per high power field, involving more than 50% of the tumor-normal tissue interface was considered significant. RESULTS: The two groups were comparable for age, gender, pre-operative carcino embryonic antigen (CEA) levels and pathological stage. Significant lymphocytic infiltration was seen in 63.6% (7 of 11) patients in the study group compared to only 8.5% (1 of 12) patients in the placebo group (P = 0.005). Despite fewer recurrences and a longer survival in the study group, the difference was not significant. CONCLUSION: This study shows that pre-operative famotidine may significantly enhance lymphocytic infiltration in colorectal cancer and may have potential for use as an anticancer agent in colorectal cancer. 相似文献