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口腔鳞状细胞癌中肿瘤浸润淋巴细胞的分子特征分析

Molecular characterisation of tumour infiltrating lymphocytes in oral squamous cell carcinoma.

作者信息

Stephens M, Lim K, Stephens P, Thomas D W, Lim S H

机构信息

Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, UK.

出版信息

Cancer Immunol Immunother. 1998 Mar;46(1):34-40. doi: 10.1007/s002620050457.

Abstract

Oral squamous cell carcinoma (OSCC) is often associated with a lymphocytic infiltrate that is believed to represent an in vivo immune reaction to the tumour cells. In this study, the tumour-infiltrating lymphocytes (TIL) associated with primary OSCC were characterised molecularly in six newly-diagnosed patients to determine the nature of the immune response to the primary tumour. The primary tumours in three of the six patients were associated with a moderate to dense CD8+ T cell infiltrate whilst the cellular infiltrate in the other primary tumours was sparse. The CD3+ T cells were also HLA-DR+. In all cases, there were few CD56+ cells, suggesting that TIL were predominantly T cells bearing the alpha/beta T cell receptors (TCR). The TCR Vbeta repertoire of TIL in these six cases was analysed. TCR Vbeta gene usage by TIL was heterogeneous. A restricted usage of TCR Vbeta genes by TIL was evident in two tumours associated with a dense CD3+ T cell infiltrate. In one of these, there was histological evidence of tumour cell destruction by TIL. Further analysis of the predominant TCR Vbeta gene family used by TIL in this individual showed a unique in-frame nucleotide sequence in 100% of the transcripts. This recurrent transcript was not detected in the peripheral blood of this patient, indicating a local T cell clonal expansion in the vicinity of the tumour. Overall, these results suggest that activation and clonal expansion of T cells occurs and may play a role in local tumour destruction in OSCC.

摘要

口腔鳞状细胞癌(OSCC)常伴有淋巴细胞浸润,这种浸润被认为代表了机体对肿瘤细胞的免疫反应。在本研究中,对6例新诊断患者的原发性OSCC相关肿瘤浸润淋巴细胞(TIL)进行了分子特征分析,以确定对原发性肿瘤免疫反应的性质。6例患者中有3例的原发性肿瘤伴有中度至密集的CD8 + T细胞浸润,而其他原发性肿瘤中的细胞浸润则较为稀疏。CD3 + T细胞也表达HLA - DR。在所有病例中,CD56 +细胞很少,这表明TIL主要是携带α/βT细胞受体(TCR)的T细胞。分析了这6例患者TIL的TCR Vβ谱系。TIL对TCR Vβ基因的使用具有异质性。在两个伴有密集CD3 + T细胞浸润的肿瘤中,TIL对TCR Vβ基因的使用明显受限。其中一个肿瘤中有TIL破坏肿瘤细胞的组织学证据。对该个体中TIL使用的主要TCR Vβ基因家族的进一步分析显示,100%的转录本中有一个独特的框内核苷酸序列。该患者外周血中未检测到这种重复转录本,表明肿瘤附近存在局部T细胞克隆扩增。总体而言,这些结果表明T细胞的激活和克隆扩增发生,并且可能在OSCC的局部肿瘤破坏中发挥作用。

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