关键词: T淋巴细胞亚群, CD4⁺/CD8⁺比值, CD4⁺调节性T细胞, 程序性死亡受体1, 结直肠癌

Abstract:

Objective To investigate the relationship between peripheral blood T lymphocyte subsets and tumor progression in patients with colorectal cancer. Methods Totally，100 newly diagnosed colorectal cancer patients in Shanghai Cancer Center of Fudan University from January to December 2023 were enrolled as colorectal cancer group. All the patients were classified into stage Ⅰ（8 cases），stage Ⅱ（47 cases），stage Ⅲ（34 cases） and stage Ⅳ（11 cases） according to TNM stages. There were 55 cases with lymphatic metastasis and 45 cases without lymphatic metastasis. Totally，80 healthy subjects were enrolled as healthy control group. Flow cytometry was used to determine the percentages of CD3⁺T cells（CD3⁺%），CD3⁺CD4⁺T cells（CD3⁺CD4⁺%），CD3⁺CD8⁺T cells（CD3⁺CD8⁺%），CD3⁺CD4^-CD8^-T cells [double-negative T cells （DNT）]（DNT%），CD4⁺CD25⁺CD127^low regulatory T cells（CD4⁺Treg%），CD3⁺PD-1⁺T cells（CD3⁺PD-1⁺%），and the CD4⁺/CD8⁺ ratio was calculated. The tumor biomarkers，carcinoembryonic antigen（CEA），carbohydrate antigen（CA）19-9，CA72-4，CA50 and CA242，were also determined. The efficacy of various indicators in determining lymphatic metastasis was evaluated by receiver operating characteristic（ROC） curve. Results Compared with healthy control group，the CD3⁺CD8⁺% in colorectal cancer group was increased（P<0.05），while the CD3⁺CD4⁺%，DNT% and CD4⁺/CD8⁺ ratio were decreased（P<0.05）. There was no statistical significance in CD3⁺% between the 2 groups（P>0.05）. There was statistical significance in CD4⁺/CD8⁺ ratio，CD4⁺Treg% and CD3⁺PD-1⁺% among colorectal cancer patients with different TNM stages（P<0.05）. Compared with colorectal cancer patients without lymphatic metastasis，colorectal cancer patients with lymphatic metastasis showed a decrease in CD4⁺/CD8⁺ ratio（P<0.001），while CD4⁺Treg% and CD3⁺PD-1⁺% were increased（P<0.001）. The area under curve（AUC） for single and combined determinations of CD4⁺/CD8⁺ ratio，CD4⁺Treg% and CD3⁺PD-1⁺% to determine lymphatic metastasis in colorectal cancer patients were 0.762，0.755，0.765 and 0.825，respectively. If taking any one of CEA，CA19-9，CA72-4，CA50 or CA242 positive as tumor biomarker positive，the patients for TNM stage Ⅰ were all negative，while the positive rates for stage Ⅱ，Ⅲ and Ⅳ were 48.9%（23/47），52.9%（18/34） and 90.9%（10/11），respectively. In patients of TNM stage Ⅱ and Ⅲ，the CD4⁺/CD8⁺ ratio in tumor biomarker positive patients was lower than that in negative patients（P<0.001），and CD4⁺Treg% was higher than that in negative patients（P<0.001）. There was no statistical significance in CD3⁺PD-1⁺%（P>0.05）. Conclusions The patients with colorectal cancer have the enhancement of immunosuppressive function，and T lymphocyte subsets have relations with tumor progression and tumor biomarker expression.

Key words: T lymphocyte subset, CD4⁺/CD8⁺ ratio, CD4⁺ regulatory T cell, Programmed death-1, Colorectal cancer