The T lymphocyte and NK cell levels in patients with malignant pleural effusion after radical resection of primary hepatocellular carcinoma

Abstract

Abstract: Objective To observe the levels of T lymphocytes and natural killer (NK) cells in patients with malignant pleural effusion after radical resection of primary liver cancer.Methods From March 2019 to March 2022, one hundred primary liver cancer patients with pleural effusion and ascites after radical resection who were admitted to the Second Hospital of Yulin City, Shaanxi Province were divided into a malignant group (n=24 cases) and a non-malignant group (n=76 cases) according to the nature of pleural effusion and ascites (i.e., malignant or benign). The levels of T lymphocytes and NK cells in pleural and ascites were detected. Receiver operating characteristic curve (ROC) was used to analyze the value of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺ and NK cell levels in the diagnosis of malignant pleural effusion. Spearman rank correlation coefficient was used to analyze the correlation between CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺ and NK cell levels and the risk of malignant pleural effusion.Results The levels of CD3⁺, CD3⁺CD4⁺ and NK cells in the malignant group were (61.2±11.3)%, (67.2±13.1)% and (20.4±3.4)%, respectively, which were significantly lower than those of (75.3±9.9)%, (73.6±8.5)%, and (24.5±3.6)% in the non-malignant group (P<0.05). The level of CD3⁺CD8⁺ cells in the malignant group was (33.2±5.5)%, which was significantly higher than that of (26.3±6.1)% in the non-malignant group (P<0.05). According to ROC analysis, the area under the curve (AUC) and 95%CI of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺ and NK cells in the diagnosis of malignant pleural effusion were 0.874 (0.814~0.925), 0.653 (0.549~0.767), 0.843 (0.780~0.905) and 0.846 (0.786~0.910), respectively (P<0.05). The risk of malignant pleural effusion after radical resection of primary liver cancer was negatively correlated with the levels of CD3⁺, CD3⁺CD4⁺ and NK cells (r=-0.625, r=-0.517, r=-0.573, P<0.05), and positively correlated with the levels of CD3⁺CD8⁺ (r=0.582, P<0.05).Conclusion Patients with malignant pleural effusion after radical resection have more serious immune dysfunction than patients with non-malignant pleural effusion, which is mainly manifested by the decrease of the proportion of CD3⁺, CD3⁺CD4⁺ and NK cells and the increase of CD3⁺CD8⁺ cells. Clinical screening of patients with high risk of malignant pleural effusion can be performed by detecting T lymphocyte subsets and NK cell levels in pleural effusion.

Key words: Primary liver cancer, Radical resection of liver cancer, Malignant hydrothorax and ascites, T lymphocytes, Natural killer cells

LI Jiao-jiao, ZHAO Yong-chang, WU Jun-xia. The T lymphocyte and NK cell levels in patients with malignant pleural effusion after radical resection of primary hepatocellular carcinoma[J]. Chinese Hepatolgy, 2023, 28(8): 924-927.

References

[1] Nakano R, Ohira M, Kobayashi T, et al. Reply: hepatectomy versus stereotactic body radiotherapy for primary early hepatocellular carcinoma: a propensity -matched analysis in a single institution. Surgery ,2019 ,165(5):1054-1057.
[2] 冯伟,汪启乐,王盛,等. 精准肝右静脉回流区扩大右后叶切除术在功能性残余肝体积比处于临界状态肝癌中的应用. 中华普通外科杂志,2021,36(5):373-375.
[3] Wei XB, Jiang YB, Zhang XP, et al. Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study. J Clin Oncol, 2019 ,37(24):2141-2151.
[4] Ekeke CN, Russell KL, Murthy P, et al. Intrapleural interleukin-2-expressing oncolytic virotherapy enhances acute antitumor effects and T-cell receptor diversity in malignant pleural disease. J Thorac Cardiovasc Surg, 2022 ,163(4):313-328.
[5] Alsugair Z, Kepenekian V, Fenouil T, et al. 5-hmC loss is another useful tool in addition to BAP1 and MTAP immunostains to distinguish diffuse malignant peritoneal mesothelioma from reactive mesothelial hyperplasia in peritoneal cytology cell-blocks and biopsies. Virchows Arch, 2022,481(1):23-29.
[6] 马泰,潘跃银,孙国平,等. 恶性胸/腹腔积液患者腔内应用贝伐珠单抗的价值及疗效影响因素分析. 中华疾病控制杂志,2017,21(7):727-731.
[7] He ZX, Wang S, Qiao GL, et al. Clinical efficacy of intra-cavitary infusions of autologous dendritic cell/cytokine-induced killer cell products for the treatment of refractory malignant pleural effusions and ascites. Am J Transl Res, 2020 ,12(7):3940-3952.
[8] 中国抗癌协会肝癌专业委员会,中华医学会肝病学分会肝癌学组,中国抗癌协会病理专业委员会,中华医学会病理学分会消化病学组,中华医学会外科学分会肝脏外科学组,中国抗癌协会临床肿瘤学协作专业委员会,全国肝胆肿瘤及移植病理协作组.原发性肝癌规范化病理诊断指南(2015年版).中华肝脏病杂志,2015,23(5):321-327.
[9] Sun YJ, Hu Y, Wan C, et al. Local biomaterial-assisted antitumour immunotherapy for effusions in the pleural and peritoneal cavities caused by malignancies. Biomater Sci,2021 ,9(19):6381-6390.
[10] Zhu ZX, Li S, Wu D, et al. High-throughput and label-free enrichment of malignant tumor cells and clusters from pleural and peritoneal effusions using inertial microfluidics. Lab Chip, 2022 ,22(11):2097-2106.
[11] Pang X, Zhang L, Liu N, et al. Combination of pegylated interferon-alpha and nucleos(t)ide analogue treatment enhances the activity of natural killer cells in nucleos(t)ide analogue experienced chronic hepatitis B patients. Clin Exp Immunol, 2020 ,202(1):80-92.
[12] Morikawa Y, Murakami M, Kondo H, et al. Natural killer cell group 7 sequence in cytotoxic cells optimizes exocytosis of lytic granules essential for the perforin-dependent, but not fas ligand-dependent, cytolytic pathway. Immunohorizons, 2021,5(4):234-245.
[13] Kasashima S, Kawashima A, Ozaki S, et al. Clinicopathological features of immunoglobulin G4-related pleural lesions and diagnostic utility of pleural effusion cytology. Cytopathology, 2019 ,30(3):285-294.
[14] 刘慧敏,刘晓利,王欣惠,等. 原发性肝癌患者外周血CD4⁺T、CD8⁺T、Tc17、Th17和Treg淋巴细胞的变化及其意义.实用肝脏病杂志,2022,25(2):255-258.
[15] Niu YR, Ye LL, Peng WB, et al. IL-26 promotes the pathogenesis of malignant pleural effusion by enhancing CD4⁺IL-22⁺ T-cell differentiation and inhibiting CD8⁺ T-cell cytotoxicity. J Leukoc Biol,2021,10(1):39-52.
[16] Tanaka K, Yanagihara T, Ikematsu Y, et al. Detection of identical T cell clones in peritumoral pleural effusion and pneumonitis lesions in a cancer patient during immune-checkpoint blockade. Oncotarget,2018 ,9(55):30587-30593.
[17] Tumino N, Martini S, Munari E, et al. Presence of innate lymphoid cells in pleural effusions of primary and metastatic tumors: functional analysis and expression of PD-1 receptor. Int J Cancer,2019 ,145(6):1660-1668.
[18] Liu CY, Chen BJ, Chuang SS, et al. Malignant effusions from extranodal NK/T-cell lymphomas are frequently of anaplastic morphology with azurophilic granules and of T-cell lineage. Diagn Cytopathol, 2020 ,48(5):453-463.
[19] Lara SH, Fernández-Fabrellas E, Samper GJ, et al. Cytotoxic natural killer subpopulations as a prognostic factor of malignant pleural effusion. Lung, 2019 ,197(1):53-60.