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.

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.

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).

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.