鼻咽癌组织与外周血CD4+CD25+调节性T细胞检测及临床意义

目的 通过检测鼻咽癌患者肿瘤组织及外周血中CD4+T、CD8+T、CD4+CD25T、CD4+CD25+T细胞的频数,寻找客观、全面评价鼻咽癌患者免疫状态的临床指标.方法 采用流式细胞术检测40例初诊鼻咽癌患者及10例正常时照鼻咽部组织和外周血CD4+T、CD8+T、CD4+CD25-T、CD4+CD25+T细胞比例.结果 鼻咽癌患者CD4+T细胞比例及CD4+/CD8+T比值均低于对照组(P<0.05),而CD8+T细胞两组间差异无统计学意义(P>0.05),但是CD4+/CD8+T比值在鼻咽癌组织与外周血间差异无统计学意义(P>0.05).鼻咽癌组织及外周血中CD4+CD25+T细胞比例都高于对照组(P<0.05),同时癌组织中该细胞比例远远高于外周血(P<0.05).在鼻咽癌组织中CD4+CD25+T细胞与CD8+T细胞、CD4+CDQ5-T细胞呈负相关(r分别为-0.70、-0.675,P<0.05),而在外周血中没有相关关系(P>0.05).在不同T(原发肿瘤大小)组间,T4组的鼻咽癌组织中CD4+CD25+T细胞分别高于T1、T2、T3各组(P<0.05).而在T1、T2、T3各组间差异无统计学意义(P>0.05);鼻咽癌中CD4+CD25+T细胞比例与患者有无淋巴结转移并无关系(P>0.05);鼻咽癌组织中Ⅲ+Ⅳ期组CD4+CD25+T细胞比例高于Ⅰ+Ⅱ期组(P<0.05),而在外周血中两组间差异无统计学意义(P>0.05).结论 CD4+CD25+T细胞与鼻咽癌病程进展无相关性,但是联合检测患者肿瘤组织及外周血中CD4+CD25+T细胞的频数并结合既往CD4+/CD8+T比值会全面反应患者免疫状态,为临床治疗提供依据.     

组织驻留CD8+T细胞在肿瘤中的研究进展

组织驻留记忆 T 细胞（ tissue-resident memory T cells,TRMs）作为一种特殊的记忆T细胞,在免疫应答中发挥着极其重要的作用。其特征是可表达归巢受体,从而具备驻留特性,因此能够驻留在外周组织器官中,当病原体侵袭时可以迅速反应。目前,TRMs（尤其是CD8+TRMs）与肿瘤的关系及其在抗肿瘤中的应用被愈加重视,一方面是CD8+TRMs可以通过分泌颗粒酶B、穿孔素和INF-γ等因子直接杀伤肿瘤细胞,另一方面一些抗肿瘤措施（如放化疗、免疫治疗等）可以使CD8+TRMs在肿瘤组织中富集,从而进一步提高治疗的效果。本文就CD8+TRMs的亚群分类、在肿瘤中如何调控形成以及其在肿瘤治疗中的作用等方面的研究进展进行综述。      

干细胞样CD8+ T细胞：肿瘤免疫疗法的新生力量

CD8+ T 细胞是抗肿瘤免疫应答的主要执行者。通过重塑CD8+ T 细胞杀伤肿瘤细胞的能力,免疫疗法已在抗肿瘤领域取得重大突破,但临床获益仅局限于部分患者和癌症类型。如何克服CD8+ T细胞功能障碍是肿瘤免疫疗法亟待解决的关键问题。近年来,多项研究揭示了CD8+ T细胞的干性调控机制,发现了干细胞样CD8+ T细胞具有自我更新和增殖能力,阐明了该细胞亚群在维持持续性肿瘤免疫治疗应答中的重要性。本文论述了干细胞样CD8+ T 细胞的分子与功能特征、CD8+ T 细胞干性的细胞内外影响因素,归纳总结了目前靶向CD8+ T细胞的干性重编程策略,进一步展望了靶向CD8+ T细胞干性程序来提高肿瘤免疫疗法疗效的思路和方法。     

结直肠腺癌中CD163+巨噬细胞、CD8+T细胞与微血管密度的相关性

摘 要：［目的］ 探讨结直肠腺癌中CD163+巨噬细胞、CD8+T细胞、微血管密度（MVD）的相关性及与患者临床病理因素的关系。［方法］ 通过免疫组化SP法检测61例结直肠腺癌癌组织及远癌组织中CD163+巨噬细胞、CD8+T细胞、CD34的表达水平,分析 CD163+巨噬细胞、CD8+T细胞、MVD的相关性及与患者临床病理因素的关系。［结果］ CD163、CD8、MVD在癌组织及远癌组织中的表达差异具有统计学意义(P均<0.001)。CD163与MVD的表达具有显著正相关性(r=0.615,P<0.001),CD8与MVD的表达具有负相关性(r=-0.320,P=0.012),CD8与CD163的表达具有显著负相关性(r=-0.370,P=0.003)。CD163+巨噬细胞与结直肠腺癌分化程度、淋巴结转移、远处转移、TNM分期相关（P<0.05）,MVD与结直肠腺癌肿瘤位置、分化程度、淋巴结转移、远处转移、TNM分期相关（P<0.05）,CD8+T细胞与患者性别、年龄、肿瘤位置、分化程度、TNM分期、淋巴转移、远处转移均无关（P>0.05）。［结论］ 联合靶向消除TAMs及促进CD8+T细胞的活化与增殖可能对结直肠癌的抗血管生成治疗有一定意义。     

CD4+CD25+调节性T细胞与CD4+T、CD8+T细胞在结直肠癌组织中的分布

 目的 分析CD4+CD25+ FOXP3+调节性T细胞（Treg）与CD4+T、CD8+T在结直肠癌（colorectal carcinoma, CRC）组织中的分布及其与临床病理特征之间的关系。方法 收集42例CRC新鲜手术标本,应用冰冻切片、免疫组织化学SP法检测肿瘤组织和癌旁组织中FOXP3+、CD4+T和CD8+T阳性细胞数。结果 CRC患者肿瘤组织中FOXP3表达水平显著升高,与癌旁组织相比差异有统计学意义（P<0.01）;中低分化组Treg细胞数明显高于高分化组（P<0.01）;淋巴结转移组Treg细胞数明显高于无淋巴结转移组（P<0.05）;癌巢内CD4+、CD8+T细胞数及CD4+/CD8+值显著低于间质（P<0.01）;Ⅲ+Ⅳ期、淋巴结转移组癌巢内CD4+/CD8+比值显著低于Ⅰ+Ⅱ期及无淋巴结转移组（P<0.05）;CRC中Treg数量与癌巢内CD4+/CD8+比值显著负相关（r=-0.605, P<0.01）。结论 CRC的发生发展可能与其癌组织局部微环境中Treg数量变化相关,肿瘤局部Treg数量的增多与T淋巴细胞亚群比例失调可能成为肿瘤免疫逃逸的机制之一。     

胆固醇代谢调控CD8+T细胞抗肿瘤作用的研究进展

CD8+T细胞又名细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL),具有直接杀死病原体感染细胞和癌细胞的作用.然而,CD8+T细胞常常丧失其效应功能,继而限制肿瘤微环境中的抗肿瘤免疫,因此,如何重新激活CD8+T细胞的抗肿瘤效力是目前需要解决的问题.最近研究发现,胆固醇代谢在肿瘤中发挥重要作用...     

LAP+CD4+T细胞在结直肠癌肿瘤微环境中的分布情况及其临床意义

目的：检测LAP+CD4+T细胞在结直肠癌患者肿瘤微环境中的分布情况,分析其与CD4+CD25+Treg及患者临床病理特征的相关性,初步探讨LAP+CD4+T细胞在结直肠癌发生、发展中的作用。方法： 收集2014年1月至2014年3月期间广西医科大学第一附属医院结直肠肛门外科收治并行手术治疗的50例结直肠癌患者临床病理资料,采集所有患者术前外周血、术中肿瘤组织和距离癌组织边缘10 cm以上的相应癌旁组织标本,同时采集本科室25例健康志愿者外周血作为对照组;流式细胞术检测各标本中LAP+CD4+T细胞和CD4+CD25+Treg的分布比例,比较结直肠癌患者与健康志愿者外周血中LAP+CD4+T细胞分布比例差异、结直肠癌肿瘤组织与相应癌旁组织中LAP+CD4+T细胞分布比例差异;分析LAP+CD4+T细胞和CD4+CD25+Treg与临床病理特征的相关性。结果： 50例结直肠癌患者和25位健康志愿者外周血及组织标本LAP+CD4+T细胞占CD4+T细胞比例,结直肠癌患者外周血\[(9.44±3.18)%\]高于正常人外周血\[(1.49±1.00)%,P=0.000\]、结直肠癌患者肿瘤组织\[（11.76±3.74）%\]高于相应癌旁组织\[（3.87±1.64）%,P=0.000\];其中肿瘤组织中LAP+CD4+T细胞的分布比例最高。肿瘤组织中LAP+CD4+T细胞与CD4+CD25+Treg细胞成正相关（r=0.327,P=0.02）;LAP+CD4+T细胞占CD4+T细胞的比例与肿瘤的TNM分期、远处转移及CEA水平相关（P<0.05）。结论：LAP+CD4+T细胞易聚集于结直肠癌肿瘤组织中,可能参与了结直肠癌的发生、发展,起到促进肿瘤生长、转移的作用。     

肿瘤外泌体对CD8+T细胞功能的影响及机制研究进展

外泌体（exosomes）是介导细胞间通讯的细胞外囊泡。它携带来源细胞的多种生物活性分子,并可将其输送给受体细胞,进而影响细胞功能。肿瘤来源外泌体可通过多种机制介导肿瘤的免疫逃逸。本文就肿瘤外泌体对肿瘤杀伤主力军CD8+T细胞的调控作用进行总结,分析其相关作用机制,以期为肿瘤免疫治疗的研发提供新的思路。     

肿瘤相关中性粒细胞的研究进展

肿瘤生长依赖肿瘤微环境,肿瘤相关中性粒细胞(TANs)是肿瘤微环境中的一种重要炎症细胞.TANs分为具有抗肿瘤效应的"N1"型和促肿瘤效应的"N2"型.因此,TANs具有对机体有利和有害的两面性.大量研究表明,TANs通过分泌细胞因子和化学因子等,影响肿瘤的生成、转移、血管生成与免疫调节.本文将从TANs的生物学特性和TANs与肿瘤发生发展、预后及治疗等方面,综述TANs和肿瘤关系的研究进展.     

肿瘤微环境与中性粒细胞相互作用关系的研究进展

摘 要：肿瘤微环境能够通过细胞因子招募大量中性粒细胞聚集到肿瘤局部,并使其极化成为肿瘤相关中性粒细胞,而肿瘤相关中性粒细胞又能重塑肿瘤微环境的组成,对肿瘤的发生、发展中起着重要作用。肿瘤微环境与中性粒细胞存在着相互影响的作用关系,文章就肿瘤微环境和中性粒细胞的相互关系作用及其机制的研究进展进行综述。     

The association between circulating tumor cells and Epstein-Barr virus activation in patients with nasopharyngeal carcinoma

Background: Circulating tumor cells (CTCs) and microemboli (CTM) are attracting increasing attention in medical biology and clinical practice. However, the clinical relevance of CTCs in nasopharyngeal carcinoma (NPC) has not yet been ascertained, and no study has focused on the influence of Epstein-Barr virus (EBV) status on CTCs in NPC patients. These issues were therefore examined. Methods: Peripheral blood samples were prospectively obtained from 33 NPC patients before treatment. CTCs and CTM were captured using the Isolation by Size of Epithelial Tumor (ISET) method. Immunohistochemistry on CK5/6 (cytokeratin5/6) and P63, as well as in situ hybridization of EBERs (EBV-encoded RNAs) were used to validate the harvested tumor cells. Results: Out of 33 NPC patients, CTCs were detected in 22 cases (66.7%), and CTM were observed in 2 cases (6.1%). CTCs were presented in all stages of NPC patients but had no association with the TNM stages (all P > 0.05). The presence of CTCs appeared to correlate with EBV activation status. Among the total NPC patients, the EBV VCA-IgA levels in CTC-positive cases were higher than that in CTC-negative cases (negative vs. positive: 3.88 vs. 4.86, P = 0.016). A similar result was observed in the patients without distant metastasis (negative vs. positive: 3.76 vs. 4.95, P = 0.009). When the number of CTCs was considered, CTC counts were found to correlate with EBV VCA-IgA (R = 0.382, P = 0.041) and EBV DNA load (R = 0.396, P = 0.033) for all NPC patients as well as NPC patients without distant metastases. Conclusions: These findings strongly suggested detectable CTCs/CTM in all stages of NPC patients and support a positive correlation between CTCs and EBV activation in NPC patients.     

CD8+T细胞耗竭发生和特征及其与肿瘤免疫治疗耐药的研究进展

免疫检查点抑制剂（immune checkpoint inhibitors,ICIs）是治疗多种肿瘤的重要手段,但耐药成为其最大难题。肿瘤免疫治疗耐药与肿瘤微环境（tumor microenvironment,TME）密切相关,TME中CD8⁺T细胞耗竭不仅持续性高表达抑制性受体（inhibitory receptors,IRs）,同时也是导致ICIs耐药的关键环节,靶向IRs为克服免疫治疗耐药提供了新思路。本文将重点对CD8⁺T细胞耗竭发生和特征及其与肿瘤免疫治疗耐药性相关的研究进行综述。     

人工抗原提呈细胞体外激活肝癌CD8+T细胞

目的:探讨人工抗原提呈细胞(artificial antigen presenting cell,aAPC)K32/4-IBBL/CD86对肝癌CD8+T细胞的活化作用。方法:磁珠法分选HLA-A 2阳性肝癌患者外周血CD8+T细胞,aAPC与CD8+T细胞按不同比例(1∶1、1∶2、1∶3)混合培养,诱导CTL。锥虫蓝拒染法测定CTL的生长曲线,MTS/PMS法检测CTL的增殖,流式细胞术检测CTL分泌IFN-γ的能力,MTT法检测CTL对人肝癌细胞株BEL7402和自体肝癌细胞的杀伤作用。结果:肝癌患者外周血CD8+T细胞经aAPC作用后,增殖能力明显增强,按1∶1、1∶2、1∶3比例混合培养后第8天分别为(21.2±2.5)×105、(17.6±3.2)×105、(15.3±2.8)×105,明显高于对照组的(8.5±0.15)×105(P<0.01),混合培养后分泌IFN-γ的CTL比例分别为(26.2±1.91)%、(21.3±1.38)%、(18.6±1.20)%,明显高于对照组的(0.1±0.02)%(P<0.01)。aAPC活化的CTL对BEL7402细胞和自体肝癌细胞的杀伤率较对照组显著增强,按1∶3混合培养后得到的CTL对BEL7402细胞和自体肝癌细胞的杀伤率分别为(21.8±4.3)%和(25.6±3.6)%,明显高于对照组的(3.8±1.8)%和(3.8±2.0)%(P<0.01);效靶比为50∶1时,1∶1混合培养组CTL对BEL7402细胞的杀伤率(56.8±3.0)%和对自体肝癌细胞的杀伤率(64.8±4.2)%明显高于1∶2混合培养组的(44.3±2.6)%、(56.1±3.4)%和1∶3混合培养组的(38.9±4.7)%、(46.2±4.7)%(P<0.05)。结论:aAPC在体外可高效活化肝癌患者CD8+T细胞,诱导CTL分泌IFN-γ,且CTL对人肝癌细胞株BEL7402和自体肝癌细胞具有明显的杀伤作用。     

Neuromedin U regulates the anti-tumor activity of CD8+ T cells and glycolysis of tumor cells in the tumor microenvironment of pancreatic ductal adenocarcinoma in an NMUR1-dependent manner

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis, which is lethal in approximately 90% of cases despite advanced standard therapies. A typical feature of PDAC is the immunosuppressive tumor microenvironment with multiple immunosuppressive factors including neurotransmitters. Recently, neuromedin U (NMU), a highly conserved neuropeptide with many physiological functions, has attracted attention for its roles in tumorigenesis and metastasis in several types of cancers. However, whether NMU affects PDAC progression remains unclear. In this study, using an orthotopic mouse model of PDAC in combination with bioinformatics analysis, we found that NMU was upregulated in tumor tissues from the patients with PDAC and positively correlated with a poor prognosis of the disease. Interestingly, knockout of the Nmu gene in mice enhanced the anti-tumor functions of tumor-infiltrating CD8⁺ T cells in an NMU receptor 1-dependent manner. Additionally, NMU promoted the glycolytic metabolism of mouse PDAC tumors. The activities of pyruvate kinase (PK) and lactate dehydrogenase (LDH), pivotal enzymes involved in the regulation of lactate production, were markedly reduced in tumor tissues from NMU-knockout mice. In vitro the presence of LDHA inhibitor can reduce the production of lactic acid stimulated by NMU, which can increase the anti-tumor activity of CD8⁺ T cells. Moreover, treatment of the pancreatic cancer cells with a phosphoinositide 3-kinase (PI3K) inhibitor diminished NMU-induced lactate production and the activities of PK and LDH, suggesting that NMU might regulate glycolysis via the PI3K/AKT pathway.     

Significance of cell-free epstein-barr virus DNA in monitoring prognosis of nasopharyngeal carcinoma

Objective It has been reported that cell-free Epstein-Barr virus (EBV-DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and comparing its significance with that of plasma VCA/lgA and EA/lgA levels. Methods E8V -DNA, VCA/lgA, and EA/lgA levels in plasma were determined in NPC patients with different prognosis after radiotherapy, including 30 distant metastatic patients, 22 local recurrence patients and 24 individuals with remission who had been followed-up for more than 2 years after treatment. EBV-DNA was determined using a real-time quantitative PCR system, and levels of VCA/lgA and EA/lgA were measured using standard immunofluorescence. In a cohort study, the indexes were determined after different radiation periods for the 20 new cases of nasopharyngeal carcinoma. Results The median plasma EBV-DNA concentration was 135,100 copies/ ml (interquartile range: 5,525-1,003 750) in metastatic group, 20,500 copies/ ml (interquartile range: 0 -58,500) in the local recurrence group and 0 copies/ml (interquartile range: 0-0) in the continuous remission group (P< 0.05). The levels of VCA/lgA and EA/lgA showed no significant differences among the different groups. The high level of EBV-DNA concentration in the metastatic group was more than that in the local recurrence group. A level of 1,000,000 copies/ml of EBV DNA was an indication of distant metastasis of the NPC patients with a sensitivity of 27.3%. However, the sensitivity was 0 in the local recurrence group. For the 20 new patients, EBV -DNA concentration gradually decreased during the radiation period. Before radiation there were 32,050 copies/ml (interquartile range: 3,880-317,750), 0 copies/ml (interquartile range: 0-14 375) after a 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) after the radiation was finished (P< 0.05). However, the levels of VCA/lgA and EA/lgA showed no significant difference. Conclusion Determination of plasma cell -free EBV -DNA level is more valuable than evaluation of VCA/lgA and EA/lgA for monitoring the prognosis of NPC patients.     

Significance of Cell-Free Epstein-Barr Virus DNA in Monitoring Prognosis of Nasopharyngeal Carcinoma

Objective  It has been reported that cell-free Epstein-Barr virus (EBV-DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and comparing its significance with that of plasma VCA/lgA and EA/lgA levels. Methods  E8V -DNA, VCA/lgA, and EA/lgA levels in plasma were determined in NPC patients with different prognosis after radiotherapy, including 30 distant metastatic patients, 22 local recurrence patients and 24 individuals with remission who had been followed-up for more than 2 years after treatment. EBV-DNA was determined using a real-time quantitative PCR system, and levels of VCA/lgA and EA/lgA were measured using standard immunofluorescence. In a cohort study, the indexes were determined after different radiation periods for the 20 new cases of nasopharyngeal carcinoma. Results  The median plasma EBV-DNA concentration was 135,100 copies/ ml (interquartile range: 5,525-1,003 750) in metastatic group, 20,500 copies/ ml (interquartile range: 0 -58,500) in the local recurrence group and 0 copies/ml (interquartile range: 0-0) in the continuous remission group (P< 0.05). The levels of VCA/lgA and EA/lgA showed no significant differences among the different groups. The high level of EBV-DNA concentration in the metastatic group was more than that in the local recurrence group. A level of 1,000,000 copies/ml of EBV DNA was an indication of distant metastasis of the NPC patients with a sensitivity of 27.3%. However, the sensitivity was 0 in the local recurrence group. For the 20 new patients, EBV -DNA concentration gradually decreased during the radiation period. Before radiation there were 32,050 copies/ml (interquartile range: 3,880-317,750), 0 copies/ml (interquartile range: 0-14 375) after a 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) after the radiation was finished (P< 0.05). However, the levels of VCA/lgA and EA/lgA showed no significant difference. Conclusion  Determination of plasma cell -free EBV -DNA level is more valuable than evaluation of VCA/lgA and EA/lgA for monitoring the prognosis of NPC patients.     

Evaluating prognostic value and relevant gene signatures of tumor microenvironment characterization in esophageal carcinoma

BackgroundTumor microenvironment (TME) cells are an important part of tumor tissues. There is increasing evidence that the TME plays a vital role in tumor prognosis, and is associated with patient survival in various kinds of malignances. To date, very little research has been conducted on how to effectively use TME to better evaluate the prognosis of patients with esophageal carcinoma (EC). The concept of a “TME score” was introduced to better distinguish the prognosis of patients.MethodsWe employed bioinformatic methods to investigate the TME infiltration patterns of 160 patients with EC from the Cancer Genome Atlas (TCGA) cohort. TME clusters were identified using k-means clustering methods with 1,000 resampling times. The significance of the survival difference among patients belonging to different TME clusters was assessed by the log-rank test and Kaplan-Meier survival curves. Correlations between immune cell types and survival were calculated by a Cox regression, and the Pearson correlation coefficient (PCC) was used to measure the relationship among different immune cell types. We classified patient into 2 subtypes based on the optimal breakpoint of TME score determined by R package maxstat.ResultsTwo TME phenotypes were defined based on the immune cell type fractions, and patients with a high TME score phenotype had a better prognosis than those with a low TME score phenotype. Kaplan-Meier analysis for differentially expressed micro ribonucleic acids (RNAs) and messenger RNAs also showed that different TME score subtypes were significantly associated with the prognosis of EC. Just as tumor mutational burden can predict the efficacy of immunotherapy, the TME score can predict the efficacy of immune checkpoint inhibitors (ICIs). The genomic alterations of 2 TME score subtypes of EC further revealed that genomic instability is prevalent in TMEs, and patients with a low TME score subtype have a more unstable chromosome status than those with a high subtype.ConclusionsThus, TME score is an emerging prognostic biomarker for predicting the efficacy of ICIs.     

NKG2D defines tumor-reacting effector CD8+ T cells within tumor microenvironment

For successful immunotherapy for cancer, it is important to understand the immunological status of tumor antigen-specific CD8⁺ T cells in the tumor microenvironment during tumor progression. In this study, we monitored the behavior of B16OVA-Luc cells in mice immunized with a model tumor antigen ovalbumin (OVA). Using bioluminescence imaging, we identified the time series of OVA-specific CD8⁺ T-cell responses during tumor progression: initial progression, immune control, and the escape phase. As a result of analyzing the status of tumor antigen-specific CD8⁺ cells in those 3 different phases, we found that the expression of NKG2D defines tumor-reacting effector CD8⁺ T cells. NKG2D may control the fate and TOX expression of tumor-reacting CD8⁺ T cells, considering that NKG2D blockade in OVA-vaccinated mice delayed the growth of the B16OVA-Luc2 tumor and increased the presence of tumor-infiltrating OVA-specific CD8⁺ T cells.     

Priming of CD8+ T cells with live C-26 colon adenocarcinoma to suppress intrahepatic tumor growth

Background. The suppression of metastatic tumor cells is important in the clinical treatment of cancer. In this study we investigated whether CD8⁺ T cells could be efficiently primed with tumor-associated antigens and then be activated to suppress metastasis. Methods. Mice were subcutaneously transplanted with colon adenocarcinoma C-26 cells for priming with tumor-associated antigens and were then challenged with tumor cells by an intraportal vein injection. The number of metastatic nodules that arose subsequently was counted macroscopically. The anti-tumor effector population was determined by treating the mice, or lymphocytes in vitro, with monoclonal antibodies to either CD4 or CD8. Results. The number of intrahepatic metastatic nodules in the primed mice was significantly less than that in the unprimed mice. (P < 0.01) The number of CD8⁺ T cells recovered from the liver in the primed and challenged mice was significantly larger than that in the unprimed and challenged mice. (P < 0.01) The anti-metastatic effect in the primed mice was not seen after the mice were treated with anti-CD8 antibody. The growth of C-26 cells in vivo was significantly suppressed by the in-vitro treatment of the tumor cells with primed CD8+ T cells obtained from the mice primed with tumor cells. Conclusions. CD8⁺ T cells were efficiently primed with C-26 tumor cells and liver metastasis was thereby suppressed. These findings suggest that C-26 cells express immunogenic tumor-associated antigens.