Expression And Clinical Significance Of Th1/Th2/Th17 Cytokines And Lymphocyte Subsets In PCNSL

Objective:We explore the expression and clinical significance of Th1/Th2/Th17 cytokines and lymphocyte subsets in patients with Primary central nervous system lymphoma（PCNSL）,and further analyze the factors that affect its prognosis to provide a more sufficient theoretical basis for the diagnosis and treatment of PCNSL.Methods:41 patients with initially diagnosed PCNSL admitted to our hospital from January2020 to June 2022 were included as the study subjects,and 96 patients with initially diagnosed no central nervous system involvement diffuse large B-cell lymphoma（non-CNSL-DLBCL）and the cytokines of and lymphocyte subsets of healthy people were used as the control group.We measured and analysed the levels of Th1/Th2/Th17cytokines and the distribution of lymphocyte subsets among patients in each group and in patients with PCNSL before and after treatment.Collect various clinical data of PCNSL patients(including gender,age,ECOG score,GCB,serum lactate dehydrogenase level（LDH）,serum albuminβ2 Microglobulin（β2-MG）,and statistically analyze the influence of various factors on the prognosis of PCNSL patients.Results:1.There were significant differences in plasma IL-1β,IL2,IL-4,IL-5,IL-6,IL-10,IL-12,IL-17,TNF-αand IFN-αlevels among different groups（P<0.05）.Paired comparison showed that the plasma levels of IL-2,IL-4,IL-5,IL-6,IL-10,IL-12,IL-17,TNF-αand IFN-αin PCNSL group were significantly higher than those in healthy control group.The level of IL-6 was significantly lower than that in non-CNSL-DLBCL group.In PCNSL group,the IL-2 of patients with remission after treatment was significantly higher than that before treatment.There were significant differences in Treg cells,CD4⁺,CD8^+,CD4⁺/CD8⁺and CD19⁺levels among groups.Pairwise comparison showed that the proportion of Treg cells in PCNSL patients was significantly higher than that in healthy controls,but not significantly different in non-CNSL-DLBCL patients,the proportion of CD8⁺T cell was significantly lower,while the proportion of CD4⁺T cell and CD4⁺/CD8⁺ratio were significantly higher than those in non-CNSL-DLBCL and healthy controls,while the proportion of CD19⁺T cell was significantly higher than non-CNSL-DLBCL patients.After effective treatment,the proportion of CD8⁺T cell significantly increased and CD4⁺/CD8⁺ratio decreased significantly.Regardless of whether the treatment was effective or not,the proportion of CD3⁺T cell significantly increased and the proportion of CD19⁺T cell decreased significantly（p<0.05）.2.Prognostic analysis:The median follow-up time for all patients with PCNSL was18（6-27）months.The overall objective remission rate（ORR）was 54%,and the disease control rate（DCR）was 59%.The 2-year PFS rate and OS rate were 58%and 66%,respectively.Univariate regression analysis showed that disease progression and survival time were significantly correlated with ECOG score,Bcl-2/c-Myc double expression and chemotherapy regimen.Multivariate COX regression analysis showed that Bcl-2/c-Myc double expression was an independent risk factor for disease progression（HR=8.343,95%CI 1.818-38.194）and an independent risk factor for survival（HR=9.181,95%CI1.108-76.167）.And R-MDT/R-MA chemotherapy regimen had longer progression-free survival time than R-BDT/R-BCT without MTX.（HR=0.175,95%CI 0.056-0.544）.Conclusion:1.There were significant differences in the levels of Th1/Th2/Th17 cytokines among PCNSL,non-CNSL-DLBCL and healthy controls,especially IL-2,which was significantly higher after treatment than that before treatment.Its detection is helpful to the diagnosis,treatment and prognosis of PCNSL.2.There were significant difference in the level of lymphocyte subsets among PCNSL,non-CNSL-DLBCL and healthy controls.After effective treatment,the proportion of CD8⁺T cell increased and the CD4⁺/CD8⁺ratio decreased,regardless of whether it was effective or not,the proportion of CD3⁺T cell increased and the proportion of CD19⁺T cell decreased.Its detection is helpful to the diagnosis,treatment and prognosis of PCNSL.3.The double expression of Bcl-2/c-Myc suggests poor prognosis.4.The HD-MTX based chemotherapy regimen seems to have a longer progression-free survival and overall survival than the chemotherapy based on Obotinib without MTX.The chemotherapy scheme based on HD-MTX may still be the first choice for PCNSL.