肾细胞癌患者肿瘤浸润淋巴细胞的流式细胞术分析

Flow cytometric analysis of tumour-infiltrating lymphocytes in patients with renal cell carcinoma.

作者信息

Kowalczyk D, Skorupski W, Kwias Z, Nowak J

机构信息

Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.

出版信息

Br J Urol. 1997 Oct;80(4):543-7. doi: 10.1046/j.1464-410x.1997.00408.x.

DOI:10.1046/j.1464-410x.1997.00408.x

PMID:9352689

Abstract

OBJECTIVE

To determine the immunophenotype of tumour-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) isolated from patients with renal cell carcinoma (RCC) and to analyse the correlations between the quantity of analysed cell subsets and the progression of the disease.

PATIENTS AND METHODS

PBL and TIL samples were obtained from 23 patients with RCC at different stages of disease. The immunophenotype of PBL and TIL was measured, and the TNM stage, tumour size, cellular type, histological grade, lymphocytic infiltration and performance status assessed.

RESULTS

The predominant mononuclear cells infiltrating the tumour, in all patients, were T lymphocytes (CD3+ median 66.9%, CD8+ median 34.6%, CD4+ median 26.7%). The cells possessing gamma/delta type T cell receptor accounted for a small fraction of the T cells in PBL and TIL (median 5.6% and 3.7%). Tumour-infiltrating T lymphocytes had a significantly higher percentage of cells expressing human leucocyte antigen (HLA) DR (median 30.9%) and CD25 (median 6.2%) antigens than the equivalent populations in peripheral blood from the same patient group (P < 0.001). The degree of T cell activation appeared to negatively correlate with the tumour stage (K = -0.3, P = 0.04). The percentage of natural killer (NK) cells among TIL (median 15.4%) did not reflect the value in PBL. The percentage of B cells in TIL was slightly lower than in PBL and accounted for 5.0% of cells. There was no relationship between the degree of lymphocytic infiltration and either tumour stage or grade but there appeared to be a positive correlation between the intensity of lymphocytic infiltration and the percentage of CD4+ cells in TIL (K = 0.5, P = 0.001). Moreover, the composition of TIL depended on tumour grade, which positively correlated with the percentage of CD8+ cells (K = 0.4, P = 0.005) and negatively with the percentage of NK cells (K = -0.5, P = 0.005). There was an inverse correlation with the percentage of gamma/delta T cells in PBL and the TIL concentration (K = -0.3, P < 0.05).

CONCLUSIONS

The TIL immunophenotype is different from PBL and is influenced by the histological grade of the tumour. The activation of TIL and its relationship with tumour progression suggests that they might be sensitized and activated by tumour cells.

摘要

目的

确定从肾细胞癌（RCC）患者中分离出的肿瘤浸润淋巴细胞（TIL）和外周血淋巴细胞（PBL）的免疫表型，并分析所分析细胞亚群数量与疾病进展之间的相关性。

患者与方法

从23例处于不同疾病阶段的RCC患者中获取PBL和TIL样本。检测PBL和TIL的免疫表型，并评估TNM分期、肿瘤大小、细胞类型、组织学分级、淋巴细胞浸润情况及体能状态。

结果

在所有患者中，浸润肿瘤的主要单核细胞为T淋巴细胞（CD3 + 中位数66.9%，CD8 + 中位数34.6%，CD4 + 中位数26.7%）。具有γ/δ型T细胞受体的细胞在PBL和TIL中的T细胞中占比很小（中位数分别为5.6%和3.7%）。肿瘤浸润T淋巴细胞中表达人类白细胞抗原（HLA）DR（中位数30.9%）和CD25（中位数6.2%）抗原的细胞百分比显著高于同一患者组外周血中的相应细胞群体（P < 0.001）。T细胞活化程度似乎与肿瘤分期呈负相关（K = -0.3，P = 0.04）。TIL中自然杀伤（NK）细胞的百分比（中位数15.4%）与PBL中的数值不符。TIL中B细胞的百分比略低于PBL，占细胞总数的5.0%。淋巴细胞浸润程度与肿瘤分期或分级均无关联，但淋巴细胞浸润强度与TIL中CD4 + 细胞百分比之间似乎呈正相关（K = 0.5，P = 0.001）。此外，TIL的组成取决于肿瘤分级，肿瘤分级与CD8 + 细胞百分比呈正相关（K = 0.4，P = 0.005），与NK细胞百分比呈负相关（K = -0.5，P = 0.005）。PBL中γ/δT细胞百分比与TIL浓度呈负相关（K = -0.3，P < 0.05）。