Expression of PD-1, LAG-3 and TIM-3 in peripheral blood T cells of patients with malignant solid tumors

Acta Universitatis Medicinalis Anhui 2020 10 v.55 1597-1605     font:big middle small

Found programs:

Authors:Yuan Yuan; Chen Jizhong; Zhu Yilin

Keywords:tumor;immunotherapy;exhausted T cells;PD-1;LAG-3;TIM-3

DOI:10.19405/j.cnki.issn1000-1492.2020.10.024

〔Abstract〕 Objective To investigate the expression of lymphocyte subsets, including CD4+T and CD8+T cells immune checkpoint molecules PD-1, LAG-3 and TIM-3 in patients with malignant solid tumors. Methods Flow cytometry(FCM) was used to detect the expression ratios of CD3-cells, CD3+T cells, CD4+T cells, CD8+T cells, CD4/CD8 ratio, B cells, NK cells and their immune checkpoints PD-1, LAG-3 and TIM-3, in peripheral blood of 30 patients with malignant solid tumors and 15 healthy controls. Meanwhile, correlation analysis was performed on lymphocyte subsets and immune checkpoints expression ratios in tumor patients. Results Compared with healthy controls, the proportion of CD3-cells in peripheral blood of tumor patients increased and the proportion of CD3+T cells decreased, but the difference was not statistically significant. Tumor patients compared with healthy controls,there were no statistically significant differences in CD4+T cell ratio(57.64%±15.52%)vs(54.69%±11.33%), CD8+T cell ratio(34.03%±14.27%)vs(31.13%±9.97%), CD4/CD8 ratio 1.94(0.96, 2.68)vs1.85(1.30, 2.67), B cell ratio 5.90%(3.09%,10.69%)vs7.63%(6.67%,10.85%). However, the proportion of NK cells decreased by 8.61%(5.58%, 16.15%)vs21.96%(12.84%, 36.47%). The expression rates of immune checkpoint molecules PD-1, LAG-3 and TIM-3 on CD4+T, CD8+T cells in tumor patients were higher than those in healthy controls, and the proportion of double positive exhausted CD4+T increased, but there was no difference in the proportion of double positive exhausted CD8+T. The proportion of CD4+T cells in tumor patients was negatively correlated with the proportion of PD-1+CD4+T cells and the proportion of double positive exhausted CD4+T cells. Conclusion The proportion of peripheral blood lymphocytes in patients with malignant solid tumors is disordered, negative immune checkpoint molecules are highly expressed and co-expressed, and the proportion of exhausted T cells increased, which negatively regulates cellular immunity. Synergistic effects of immune checkpoint molecules may be involved in the development of tumors. Multi-target combination therapy may yield better results in cancer patients whose immunocheckpoint inhibitors have failed single drug therapy.