| Background and ObjectivesExtranodal natural killer/T cell lymphoma(ENKTL)is the most common type of non-Hodgkin's lymphoma(NHL)in the primary nasal cavity and is closely related to EB virus infection.The incidence of ENKTL is high in China,but there is no unified treatment standard,and the survival of patients is very different.Therefore,it is necessary to explore some reliable markers to evaluate the prognosis of patients as early as possible,and to guide the clinical practice of individualized and accurate treatment.The target therapy for "immune checkpoint" has benefited many tumor patients,but the expression and prognostic value of "immune checkpoint" in ENKTL not clear.Therefore,we aim to explore the expression and prognostic value of Programmed cell death-1(PD-1),T cell immunoglobulin domain mucin-3(TIM-3),Lymphocyte activation gene-3(LAG-3),B and T lymphocyteattenuator(BTLA)in ENKTL tissues,and new targets for ENKTL immunotherapy.Materials and Methods1.34 cases of ENKTL confirmed by histopathology were selected from November 2013 to December 2018 in the People's Hospital of Zhengzhou University as experimental group and 9 cases of nasal inflammatory tissue as control group;2.Collect the patient's clinical data,including:age,sex,location of primary lesion,number of lymph node invasion,results of biochemical routine examination,treatment plan,etc.,parallel Ann Arbor stage,IPI score,PINK score,etc;3.Immunohistochemical method was used to detect the expression of PD-1?TIM-3?LAG-3 and BTLA in tissue samples;4.Apply SPSS25.0 software to perform correlation analysis and prognostic analysis of PD-1,TIM-3,LAG-3,BTLA and clinical features,and draw survival curves.Rusults1.PD-1,TIM-3,LAG-3 and BTLA all can be expressed in different degrees in ENKTL tissues,with positive rates of 50%(17/34),64.7%(22/34),44.1%(15/34),91.2%(31/34);2.In case-control experiment:among the 34 cases of ENKTL,25 were males and 9 were females,with a median age of 46(27-75)years,and among the 9 cases of rhinitis group,7 were males and 2 were females,with a median age of 51(27-68)years old.There were significant differences in the expression of TIM3 and LAG3 between the two groups(?2=6.203,P=0.013;?2=4.310,P=0.038).3.In ENKTL tissues,the expression of PD-1 and TIM-3 was significantly positively correlated(r=0.492,P=0.003);4.The primary serum lymphocyte count(ALC),globulin distribution were statistically significant between PD1 negative and positive groups(U=203.000,P=0.045;U=213.000,P=0.018);There was a statistically significant difference in patients' gender betweenr TIM3 expressed and non-expressed group(P=0.04);The count of platelets and ALC varied significantly between the LAG3 positive and negative groups(U=213.000,P-0.014;U=203.000,P=0.036);The newly diagnosed mononuclear cell count(AMC),OS time and PFS time was significantly different between the BTLA negative and positive groups(U=78.500,P=0.049;U=12.000,P=0.034;U=13,P=0.041);5.There was a statistical correlation between the degree of PD-1 or PD-1/BTLA expression and the PFS and OS time of patients(P=0.025;P=0.037);6.Ann Arbor stage ?,lymphocyte/mononuclear ratio(LMR)<4.343,EBV-DNA copies greater than normal,and TIM-3 positive was an independent prognostic factors for ENKTL.Conclusions1.PD-1,TIM-3,LAG-3 and BTLA all can be expressed in the tissues of ENKTL;and the positive rates of TIM-3 and LAG-3 are significantly different from those of rhinitis group;2.In ENKTL tissues,the expression of PD-1 and TIM-3 was significantly positively correlated;3.There was a statistical correlation between the degree of PD-1 or PD-1/BTLA expression and the survival time of patients;4.TIM-3 was an independent poor prognostic factor of ENKTL. |
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