摘要
背景:肿瘤浸润淋巴细胞(TILs)是胰管腺癌(PDAC)肿瘤微环境的主要参与者之一。然而,TIL与肿瘤的相互作用机制复杂,目前尚不清楚。目的:评价PDAC组织中的免疫反应状况,探讨这些指标在大样本中的预后价值,为PDAC的免疫治疗提供新的理论依据。方法:对143例PDAC患者的组织芯片(TMA)进行CD4和CD8 T细胞免疫组化染色。以PDAC组织中CD4 T细胞和CD8 T细胞空间分布的两个主要变量(上皮内侵袭和肿瘤内浸润)作为评价免疫反应状态的指标,并分析其与临床病理因素的相互关系。结果:我们的资料显示,上皮内CD4 T和CD8 T的侵袭率均低于肿瘤内浸润。CD8 T上皮内病变和肿瘤内浸润较CD4 T强,CD8 T上皮内病变是影响整体生存的独立预后因素,与血管浸润呈负相关,与CD4 T和CD8 T高浸润呈正相关。CD8 T高浸润,无CD8 T上皮内病变,是影响预后的一个不良因素。CD8 T高浸润伴T分期进展。因此,在PDAC进展过程中,CD4和CD8免疫反应出现T细胞失衡。CD8 T上皮内病变是一种独立的良好预后指标,而CD4 T的上皮内病变和CD8 T和CD4 T的瘤内浸润则起着模糊的作用。结论:在高T细胞浸润无攻击的肿瘤微环境中,增加CD8 T细胞的上皮内侵袭数是一种新的免疫抑制机制,是一种潜在的肿瘤免疫治疗方法。
关键词: 胰腺癌,CD8 T淋巴细胞,CD4 T淋巴细胞,肿瘤微环境,预后指标,PDAC。
Current Molecular Medicine
Title:Intraepithelial Attack Rather than Intratumorally Infiltration of CD8+T Lymphocytes is a Favorable Prognostic Indicator in Pancreatic Ductal Adenocarcinoma
Volume: 17 Issue: 10
关键词: 胰腺癌,CD8 T淋巴细胞,CD4 T淋巴细胞,肿瘤微环境,预后指标,PDAC。
摘要: Background: Tumor-infiltrating lymphocytes (TILs) are one of the major participants in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of interaction between TILs and tumors is complex and remains unclear.
Objective: To evaluate the state of immunoreactions in PDAC tissues, and explore the prognostic value of these markers in a large sample, to provide a new theoretical basis for PDAC immunotherapy.
Method: Immunohistochemical staining of CD4+ and CD8+T cells was performed in a tissue microarray (TMA) of 143 cases of PDAC. Two major variables for the spatial distributions of CD4+T and CD8+T cells in PDAC tissues, intraepithelial attack and intratumoral infiltration, were used to evaluate the state of immunoreactions, and the interrelationships with the clinicopathological variables were analyzed.
Results: Our data showed that both the intraepithelial CD4+T and CD8+T attack were less frequent than the intratumoral infiltration. CD8+T intraepithelial attack and intratumoral infiltration were more intense than CD4+T. CD8+T intraepithelial attack was an independent favorable prognostic factor for overall survival, correlating negatively with vascular invasion and positively with CD4+T and CD8+T high intratumoral infiltration. CD8+T high intratumoral infiltration without CD8+T intraepithelial attack was a poor prognostic factor. CD8+T high intratumoral infiltration was accompanied by T stage progression. Conclusively, in PDAC progression, imbalances of T cells occurred in CD4+ and CD8+ immunoreactions. The CD8+T intraepithelial attack was an independent favorable prognostic indicator, however the intraepithelial attack of CD4+T and the both intratumoral infiltration of CD8+T and CD4+T played an ambiguous role.
Conclusion: Our data suggested that it is a potential approach to increasing the number of intraepithelial attacking CD8+T cells for tumor immunotherapy, and exploring a new mechanism for immunosuppression in a tumor microenvironment with high T cell infiltration without attack.
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Intraepithelial Attack Rather than Intratumorally Infiltration of CD8+T Lymphocytes is a Favorable Prognostic Indicator in Pancreatic Ductal Adenocarcinoma, Current Molecular Medicine 2017; 17 (10) . https://dx.doi.org/10.2174/1566524018666180308115705
DOI https://dx.doi.org/10.2174/1566524018666180308115705 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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