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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2026, Vol. 19 ›› Issue (03) : 418 -423. doi: 10.3877/cma.j.issn.1674-6902.2026.03.010

论著

肺良性结节及肺癌患者外周血T淋巴细胞PD-1及CD28表达特征分析
黑若萱1, 李思敏1, 刘丽1, 陈延伟2, 李自越1,†()   
  1. 1710038　西安，空军军医大学唐都医院检验科
    2710038　西安，空军军医大学唐都医院呼吸内科
  • 收稿日期:2025-05-15 出版日期:2026-06-25
  • 通信作者: 李自越
  • 基金资助:
    国家自然科学基金面上项目(82070096)

Analysis of the expression characteristics of PD-1 and CD28 on T lymphocytes in patients with pulmonary nodules and lung cancer

Ruoxuan Hei1, Simin Li1, Li Liu1, Yanwei Chen2, Ziyue Li1,†()   

  1. 1Department of Clinical Laboratory, Second Hospital of the Air Force Medical University, Xian 710038, China
    2Department of Respiratory Medicine, Second Hospital of the Air Force Medical University, Xian, 710038, China
  • Received:2025-05-15 Published:2026-06-25
  • Corresponding author: Ziyue Li
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引用本文：

黑若萱, 李思敏, 刘丽, 陈延伟, 李自越. 肺良性结节及肺癌患者外周血T淋巴细胞PD-1及CD28表达特征分析[J/OL]. 中华肺部疾病杂志(电子版), 2026, 19(03): 418-423.

Ruoxuan Hei, Simin Li, Li Liu, Yanwei Chen, Ziyue Li. Analysis of the expression characteristics of PD-1 and CD28 on T lymphocytes in patients with pulmonary nodules and lung cancer[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2026, 19(03): 418-423.

目的

分析肺良性结节以及肺癌患者T细胞程序性死亡受体1(programmed death-1, PD-1)以及CD28分子表达特征及差异。

方法

纳入2024年1月至2024年12月就诊于空军军医大学第二附属医院55例肺良性结节患者为对照组，586例肺癌患者为观察组。采用流式细胞术检测外周血T细胞表面PD-1/CD28表达，电化学发光检测血清肿瘤标志物。

结果

良性组CD3＋PD-1＋ T细胞比率[19.16%(14.66%，26.09%)]比较肺癌组[21.01%(16.00%，26.70%)]，差异无统计学意义(P>0.05)；良性组CD3＋CD4＋PD-1＋ T细胞比率及计数[22.76%(16.87%，28.38%)，125(93，161)个/μl]低于肺癌组[24.8%(19.17%，32.02%)，114(77，160)个/μl](P<0.05)；良性组CD3＋CD28＋，CD3＋CD4＋CD28＋及CD3＋CD8＋CD28＋ T细胞绝对计数[475(345，612)个/μl, 378(270，490)个/μl, 84(60，132)个/μl]低于肺癌组[390(277，539)个/μl, 303(212，425)个/μl, 72(44，109)个/μl]下降(P<0.05)。肺癌组血清肿瘤标志物水平癌胚抗原(CEA) [3.24(1.88，7.83)ng/ml]、铁蛋白(FER) [238.5(129.3，416.8)μg/ml]、神经元特异性烯醇化酶(NSE)[16.3(13.15，21.65)ng/ml]、糖类抗原125(CA125) [17.4(11.7，33.95)U/ml]、细胞角蛋白19的可溶性片段抗原21-1(CYFRA21-1) [2.71(1.86，4.44)ng/ml]、糖类抗原50(CA50) [9.05(6.25，12.72)U/ml]高于良性组2.06(1.3，3.05)ng/ml、139(88，214)μg/ml、13.6(11，16.6)ng/ml、9.61(7.53，14.6)U/ml、2.03(1.6，2.87)ng/ml、6.39(5.24，8.49)U/ml(P<0.05)。

结论

肺癌患者比较肺良性结节患者PD-1＋ T细胞比率升高，CD28＋ T细胞数量减少，表明肺癌患者体内的T细胞免疫抑制状态，PD-1及CD28阳性T细胞的持续改变可能与肺癌发展密切相关。

关键词: 肺良性结节, 支气管肺癌, T淋巴细胞, 程序性死亡受体1, CD28分子
Objective

Programmed death-1(PD-1) is a T-cell inhibitory molecule, while CD28 serves as a T-cell co-stimulatory molecule. This study aimed to comprehensively analyze the expression patterns and differences of PD-1 and CD28 on T cells in patients with benign pulmonary nodules and lung cancer.

Methods

A total of 55 patients with benign pulmonary nodules and 586 patients with lung cancer from the Second Affiliated Hospital of Air Force Medical University were enrolled. Flow cytometry was utilized to assess the surface expression of PD-1 and CD28 on peripheral blood T cells, while electrochemiluminescence was employed to measure serum tumor markers.

Results

Compared with the control group at 15.22% (10.75%, 18.63%), the ratio of CD3+ PD-1+ T cells was significantly increased in the benign group at 19.16% (14.66%, 26.09%) and the lung cancer group at 21.01% (16.00%, 26.70%), but there was no statistical significance between the lung cancer group and the benign group (P>0.05). The ratio and count of CD3+ CD4+ PD-1+ T cells in the benign group at 22.76% (16.87%, 28.38%) and 125 (93, 161) cells/μl, and in the lung cancer group at 24.8% (19.17%, 32.02%) and 114 (77, 160) cells/μl were significantly higher than those in the control group at 17.46% (11.62%, 22.31%) and 92 (68, 134) cells/μl (P<0.05). Compared with the benign group at 475 (345, 612) cells/μl; 378 (270, 490) cells/μl; 84 (60, 132) cells/μl, the absolute counts of CD3+ CD28+ , CD3+ CD4+ CD28+ , and CD3+ CD8+ CD28+ T cells in the lung cancer group at 390 (277, 539) cells/μl; 303 (212, 425) cells/μl; 72 (44, 109) cells/μl were significantly decreased (P<0.05). The levels of serum tumor markers in the lung cancer group, including CEA 3.24 (1.88, 7.83) ng/ml, FER 238.5 (129.3, 416.8) μg/ml, NSE 16.3 (13.15, 21.65) ng/ml, CA125 17.4 (11.7, 33.95) U/ml, CYFRA21-1 2.71 (1.86, 4.44) ng/ml, and CA50 9.05 (6.25, 12.72) U/ml, were significantly higher than those in the benign group at 2.06 (1.3, 3.05) ng/ml; 139 (88, 214) μg/ml; 13.6 (11, 16.6) ng/ml; 9.61 (7.53, 14.6) U/ml; 2.03 (1.6, 2.87) ng/ml and 6.39 (5.24, 8.49) U/ml (P<0.05). There was no significant correlation between the ratio of PD-1 or CD28 positive T cells and the levels of tumor markers (P>0.05).

Conclusion

Compared with the healthy and benign pulmonary nodule groups, the proportion of PD-1+ T cells was markedly increased in lung cancer patients, whereas the number of CD28+ T cells was significantly decreased. These findings suggest an immune-inhibitory state of T cells in lung cancer patients, and the continuous alterations in PD-1 and CD28-positive T cells may be closely associated with the progression of lung cancer.

Key words: Benign pulmonary nodules, Lung carcinoma, T lymphocytes, PD-1, CD28 molecule
表1 PD1阳性T淋巴细胞差异分析M(P25, P75)
检测指标 对照组(n＝55) 观察组(n＝586) U值 P值
CD3＋PD1＋% 19.16(14.66，26.09) 21.01(16，26.7) 13 920 0.094
CD3＋CD4＋PD1＋% 22.76(16.87，28.38) 24.80(19.17，32.02) 13 947 0.098
CD3＋CD8＋PD1＋% 17.63(10.84，26.63) 19.47(13.18，28.63) 14 310 0.170
CD3＋PD1＋ 201(141，280) 179(122，249) 14 102 0.126
CD3＋CD4＋PD1＋ 125(93，161) 114(77，160) 14 371 0.184
CD3＋CD8＋PD1＋ 63(41，104) 60(38，93) 14 675 0.273
表2 CD28阳性T淋巴细胞差异分析M(P25, P75)
检测指标 对照组(n＝55) 观察组(n＝586) U值 P值
CD3＋CD28＋ % 44.7(34.2，52.65) 45.88(37，56.77) 15 000 0.397
CD3＋CD4＋CD28＋ % 70.02(54.47，79.2) 69.36(58.78，79.58) 15 748 0.780
CD3＋CD8＋CD28＋ % 23.68(16.21，30.26) 23.58(15.35，32.56) 15 898 0.869
CD3＋CD28＋ 475(345，612) 390(277，539) 12 418 0.005
CD3＋CD4＋CD28＋ 378(270，490) 303(212，425) 12 695 0.009
CD3＋CD8＋CD28＋ 84(60，132) 72(44，109) 12 753 0.010
表3 两组患者外周血肿瘤标志物差异分析M(P25, P75)
检测指标 对照组(n＝381) 观察组(n＝586) U值 P值
CEA( ng/ml) 2.06(1.3，3.05) 3.24(1.88，7.83) 17 147 0.001
FER(μg/ml) 139(88，214) 238.5(129.3，416.8) 18 678 0.001
NSE(ng/ml) 13.6(11，16.6) 16.3(13.15，21.65) 9 128 0.001
CA125(U/ml) 9.61(7.53，14.6) 17.4(11.7，33.95) 7 095 0.001
CYFRA21-1(ng/ml) 2.03(1.6，2.87) 2.71(1.86，4.44) 9 444 0.001
CA50(U/ml) 6.39(5.24，8.49) 9.05(6.25，12.72) 9 652 0.001
SCC(ng/ml) 0.56(0.47，0.68) 0.57(0.43，0.79) 13 885 0.673
表4 PD1/CD28阳性T细胞比率与肿瘤标志物水平相关性分析
检测指标 CD3＋PD1＋% CD4＋PD1＋% CD8＋PD1＋% CD3＋CD28＋% CD4＋CD28＋% CD8＋CD28＋%
r P r P r P r P r P r P
CEA －0.028 0.522 0.022 0.627 －0.036 0.414 －0.036 0.415 －0.020 0.658 －0.051 0.253
FER 0.006 0.900 0.016 0.724 －0.010 0.823 －0.077 0.083 －0.006 0.900 －0.045 0.304
NSE 0.020 0.648 0.002 0.964 0.071 0.111 －0.002 0.962 0.035 0.425 －0.032 0.464
CA125 0.026 0.558 0.061 0.166 0.014 0.750 －0.100 0.054 －0.044 0.324 －0.113 0.050
CYFRA21-1 0.039 0.383 0.039 0.374 0.057 0.201 －0.106 0.057 －0.053 0.232 －0.083 0.060
CA50 0.047 0.291 0.045 0.314 0.025 0.575 －0.054 0.220 －0.019 0.673 －0.096 0.059
SCC 0.048 0.281 0.060 0.175 －0.015 0.736 －0.059 0.184 －0.054 0.220 －0.071 0.107
图1 肺结节及肺癌患者影像资料
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