肿瘤内肿瘤浸润淋巴细胞与中性粒细胞与淋巴细胞比值的关联是非小细胞肺癌的独立预后因素。

Association of intra-tumoral tumour-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio is an independent prognostic factor in non-small cell lung cancer.

作者信息

Dirican Nigar, Karakaya Yeliz Arman, Gunes Sedat, Daloglu Ferah Tuncel, Dirican Ahmet

机构信息

Department of Chest Diseases, Suleyman Demirel University of Medicine, Isparta, Turkey.

Department of Pathology, Isparta State Hospital, Isparta, Turkey.

出版信息

Clin Respir J. 2017 Nov;11(6):789-796. doi: 10.1111/crj.12417. Epub 2015 Dec 28.

DOI:10.1111/crj.12417

PMID:26619201

Abstract

BACKGROUND

Studies suggest that tumour-infiltrating lymphocytes (TILs) and inflammation markers have independent roles in non-small cell lung cancer (NSCLC), but the relationship between the two pronostic factors remains unclear. In this study, we investigated TILs and inflammation markers in with patients advanced stage NSCLC and assessed the association of their levels with prognosis.

MATERIALS AND METHODS

TILs were evaluated by immunohistochemical staining for cluster of differentiation 3 (CD3) and cluster of differentiation 5 (CD5) and by hematoxylin and eosin staining for non-specific lymphocyte. We investigated the localisation pattern of TILs in advanced stage NSCLC. We divided all cases into two groups: TILs-high and TILs-low groups, by 75th percentile of the population of. In our study, inflammation markers were assessed by C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR).

RESULTS

The results showed that the presence of intra-tumoral high CD3 and low CD5 were an independent prognostic factor for overall survival (respectively, P = 0.022 and P = 0.025). Moreover, the high NLR and serum high CRP levels were associated with poor survival (respectively, P = 0.008; P = 0.027). In multi-variate survival analysis, the high CD3 , low CD5 , high NLR, tumour node metastasis (TNM) stage, depth of tumour invasion and lymph node metastasis remained independent prognostic factors (respectively, P = 0.018, P = 0.020, P = 0.024, P = 0.038, P = 0.020 and P = 0.047).The high NLR was detected negative correlation with intra-tumoral CD3 and positive correlation with intra-tumoral CD5 (respectively, r = -0.623, P = 0.012; r = 0.628, P = 0.028).

CONCLUSIONS

This study is first report demonstrating the prognostic value of intra-tumoral low CD5 with NSCLC. Increased CD3 and low CD5 was observed in patients with poor prognosis; the two molecules were correlated with NLR, suggesting that inflammation might be used as improve therapeutic efficacy to immunotherapy for advanced NSCLC.

摘要

背景

研究表明，肿瘤浸润淋巴细胞（TILs）和炎症标志物在非小细胞肺癌（NSCLC）中具有独立作用，但这两个预后因素之间的关系仍不清楚。在本研究中，我们调查了晚期NSCLC患者的TILs和炎症标志物，并评估了它们的水平与预后的关联。

材料与方法

通过免疫组织化学染色检测分化簇3（CD3）和分化簇5（CD5）来评估TILs，通过苏木精和伊红染色检测非特异性淋巴细胞。我们研究了晚期NSCLC中TILs的定位模式。我们将所有病例分为两组：TILs高组和TILs低组，以人群的第75百分位数为界。在我们的研究中，炎症标志物通过C反应蛋白（CRP）和中性粒细胞与淋巴细胞比值（NLR）进行评估。

结果

结果显示，肿瘤内高CD3和低CD5的存在是总生存期的独立预后因素（分别为P = 0.022和P = 0.025）。此外，高NLR和血清高CRP水平与较差的生存率相关（分别为P = 0.008；P = 0.027）。在多变量生存分析中，高CD3、低CD5、高NLR、肿瘤淋巴结转移（TNM）分期、肿瘤浸润深度和淋巴结转移仍然是独立的预后因素（分别为P = 0.018、P = 0.020、P = 0.024、P = 0.038、P = 0.020和P = 0.047）。高NLR与肿瘤内CD3呈负相关，与肿瘤内CD5呈正相关（分别为r = -0.623，P = 0.012；r = 0.628，P = 0.028）。