结核分枝杆菌感染对非小细胞肺癌患者调节性免疫细胞的负向调节作用

doi:10.3877/cma.j.issn.1674-6880.2019.04.005

目的

探讨结核分枝杆菌感染对非小细胞肺癌患者调节性免疫细胞的负向调节作用。

方法

选择2014年3月到2018年3月温州市中心医院就诊的非小细胞肺癌合并结核分枝杆菌感染患者为感染组（10例），单纯非小细胞肺癌患者为肿瘤组（10例），同期选择10例健康体检者为对照组。采用免疫组织化学法检测Ki-67增殖水平；采用流式细胞术检测CD4⁺CD25⁺Foxp3⁺调节性T（Treg）细胞和CD19⁺IL-10⁺调节性B（Breg）细胞的比例。

结果

肿瘤组Ki-67的比例为（35 ± 4）%，感染组为（66 ± 6）%，感染组Ki-67的比例显著高于肿瘤组（t = 4.068，P < 0.001）。三组肺癌合并结核患者外周血CD4⁺CD25⁺Foxp3⁺Treg细胞、CD19⁺IL-10⁺Breg细胞比例的比较，差异均有统计学意义（F = 69.400，P < 0.001；F = 16.090，P < 0.001）。且与肿瘤组CD4⁺CD25⁺Foxp3⁺Treg细胞比例[（0.41 ± 0.03）%、（0.21 ± 0.03）%、（1.03 ± 0.08）%]、CD19⁺IL-10⁺Breg细胞比例[（0.429 ± 0.021）%、（0.268 ± 0.013）%、（0.783 ± 0.111）%]比较，对照组均显著降低，而感染组均显著升高（P均< 0.05）。

结论

非小细胞肺癌合并结核分枝杆菌感染患者外周血中Treg细胞和Breg细胞比例显著升高。

关键词: 分枝杆菌，结核, 感染, 癌，非小细胞肺, 免疫，细胞

Objective

To investigate the effect of Mycobacterium tuberculosis infection on regulatory immune cells in patients with non-small cell lung cancer (NSCLC).

Methods

The NSCLC patients in Wenzhou Central Hospital between March 2014 and March 2018 were selected as the infection group (n = 10) and cancer group (n = 10) according to whether suffering from Mycobacterium tuberculosis infection. Ten healthy subjects were enrolled as the control group at the same time. The proliferation level of Ki-67 was detected by immunohistochemistry. The flow cytometry was used to detect CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells and CD19⁺IL-10⁺ regulatory B (Breg) cells.

Results

The proportion of Ki-67 was (35 ± 4)% in the cancer group and (66 ± 6)% in the infection group; it was much higher in the infection group than in the cancer group (t = 4.068, P < 0.001). The proportion of CD4⁺CD25⁺Foxp3⁺Treg cells and CD19⁺IL-10⁺Breg cells among three groups all showed significant differences (F = 69.400, P < 0.001; F = 16.090, P < 0.001). Compared with the cancer group, the proportion of CD4⁺CD25⁺Foxp3⁺Treg cells [(0.41 ± 0.03)%, (0.21 ± 0.03)%, (1.03 ± 0.08)%] and CD19⁺IL-10⁺Breg cells[(0.429 ± 0.021)%, (0.268 ± 0.013)%, (0.783 ± 0.111)%] decreased markedly in the control group, and increased obviously in the infection group (all P < 0.05).

Conclusion

The proportion of Treg and Breg cells in peripheral blood of NSCLC patients with tuberculosis infection is significantly higher.

Key words: Mycobacterium tuberculosis, Infection, Carcinoma, non-small-cell lung, Immunity, cellular

图1 非小细胞肺癌合并结核患者结核感染部位HE染色和抗酸染色结果

图2 肿瘤组和感染组患者癌细胞病理图

图3 各组患者Treg细胞比例的比较（n = 10）

图4 各组患者外周血Breg细胞比例的比较（n = 10）

1	Chen X, Zhang LW, Huang JJ, et al. Long-term exposure to urban air pollution and lung cancer mortality: a 12-year cohort study in Northern China[J]. Sci Total Environ, 2016 (571): 855-861.
2	Olea-Popelka F, Muwonge A, Perera A, et al. Zoonotic tuberculosis in human beings caused by Mycobacterium bovis-a call for action[J]. Lancet Infect Dis, 2017, 17 (1): e21-e25.
3	Hong S, Mok Y, Jeon C, et al. Tuberculosis, smoking and risk for lung cancer incidence and mortality[J]. Int J Cancer, 2016, 139 (11): 2447-2455.
4	Kim YK, Lee KS, Kim BT, et al. Mediastinal nodal staging of nonsmall cell lung cancer using integrated 18F-FDG PET/CT in a tuberculosis-endemic country: diagnostic efficacy in 674 patients[J]. Cancer, 2007, 109 (6): 1068-1077.
5	Ercegovac M, Subotic D, Zugic V, et al. Postoperative complications do not influence the pattern of early lung function recovery after lung resection for lung cancer in patients at risk[J]. J Cardiothorac Surg, 2014 (9): 92.
6	Chinen T, Kannan AK, Levine AG, et al. An essential role for the IL-2 receptor in Treg cell function[J]. Nat Immunol, 2016, 17 (11): 1322-1333.
7	Gerriets VA, Kishton RJ, Johnson MO, et al. Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression[J]. Nat Immunol, 2016, 17 (12): 1459-1466.
8	Dyck L, Wilk MM, Raverdeau M, et al. Anti-PD-1 inhibits Foxp3⁺ Treg cell conversion and unleashes intratumoural effector T cells thereby enhancing the efficacy of a cancer vaccine in a mouse model[J]. Cancer Immunol Immunother, 2016, 65 (12): 1491-1498.
9	Rossetti M, Spreafico R, Consolaro A, et al. TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis[J]. Ann Rheum Dis, 2017, 76 (2): 435-441.
10	Jiang T, Ren S, Li X, et al. The changing diagnostic pathway for lung cancer patients in Shanghai, China[J]. Eur J Cancer, 2017 (84): 168-172.
11	Zhang B, Zhang Y, Yu D. Lung cancer gene therapy: transferrin and hyaluronic acid dual ligand-decorated novel lipid carriers for targeted gene delivery[J]. Oncol Rep, 2017, 37 (2): 937-944.
12	Amreddy N, Babu A, Muralidharan R, et al. Polymeric nanoparticle-mediated gene delivery for lung cancer treatment[J]. Top Curr Chem (Cham), 2017, 375 (2): 35.
13	Zheng QW, Zhou YL, You QJ, et al. WWOX inhibits the invasion of lung cancer cells by downregulating RUNX2[J]. Cancer Gene Ther, 2016, 23 (12): 433-438.
14	Lin J, Wang Y, Zou YQ, et al. Differential miRNA expression in pleural effusions derived from extracellular vesicles of patients with lung cancer, pulmonary tuberculosis, or pneumonia[J]. Tumour Bio, 2016. [Epub ahead of print]
15	Dagaonkar RS, Choong CV, Asmat AB, et al. Significance of coexistent granulomatous inflammation and lung cancer[J]. J Clin Pathol, 2017, 70 (4): 337-341.
16	Koyama K, Kagamu H, Miura S, et al. Reciprocal CD4⁺ T-cell balance of effector CD62Llow CD4⁺ and CD62LhighCD25⁺ CD4⁺ regulatory T cells in small cell lung cancer reflects disease stage[J]. Clin Cancer Res, 2008, 14 (21): 6770-6779.
17	Whiteside TL. What are regulatory T cells (Treg) regulating in cancer and why?[J]. Semin Cancer Biol, 2012, 22 (4): 327-334.
18	Young MR, Levingston CA, Johnson SD. Treatment to sustain a Th17-type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer[J]. Int J Cancer, 2016, 138 (10): 2487-2498.
19	Bos PD. TREG cells in cancer: beyond classical immunological control[J]. Immunol Invest, 2016, 45 (8): 721-728.
20	Wang Z, Cheng Q, Tang K, et al. Lipid mediator lipoxin A4 inhibits tumor growth by targeting IL-10-producing regulatory B (Breg) cells[J]. Cancer Lett, 2015, 364 (2): 118-124.
21	Inoue S, Scott D, Golding B, et al. Regulatory B cells inhibit antitumor immunity[J]. Cancer Res, 2007, 67 (10): 5059.
22	Lindner S, Dahlke K, Sontheimer K, et al. Interleukin 21-induced granzyme B-expressing B cells infiltrate tumors and regulate T cells[J]. Cancer Res, 2013, 73 (8): 2468-2479.

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Negative regulation of Mycobacterium tuberculosis infection on regulatory immune cells in patients with non-small cell lung cancer

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Negative regulation of Mycobacterium tuberculosis infection on regulatory immune cells in patients with non-small cell lung cancer