Evaluation And Clinical Significance Of PD-L1、IDO And Tumor-Infiltrating Lymphocytes In Microenvironment Of Thymic Squamous Cell Carcinoma

Objective:To detect the expression and infiltration of PD-L1,IDO and tumor-infiltrating lymphocytes(TILs)in thymic squamous cell carcinoma(TSCC)tissues,analyze the correlation between the three and their relationship with clinicopathological features and patient prognosis.Method:Sixty cases of TSCC resected surgically are collected in department of Pathology,the Second Affiliated Hospital of Air Medical University from March 2017 to November 2021,then,the expression of PD-L1 and IDO and the infiltration of TILs(CD4,CD8,CD20,CD21,CD56,CD68,and FOXP3)in TSCC tissues are detected by immunohistochemistry,and the number of TILs positive cells is counted by Image-Pro Plus 6.0 software.Finally,SPSS 25.0 is used for statistical analysis.Results:1.PD-L1≥1%is defined as positive,PD-L1 is positive in 48 patients with TSCC(80%,48/60),and the positive rate is positively correlated with tumor size(X~2=4.314,P=0.038)and Masaoka-Koga stage(X~2=7.172,P=0.046);it is not correlated with gender(X~2=0.6,P=0.439),age(X~2=0.039,P=0.843),lymph node metastasis(X~2=0.104,P=0.747),surgical resection margin status(X~2=0.139,P=0.709),preoperative treatment(X~2=1.776,P=0.183),and postoperative treatment(X~2=3.158,P=0.484);in addition,it is positively correlated with CD20 positive cells infiltration in the stroma and tumor(X~2=5.424,P=0.02;X~2=11.279,P=0.001),but not with other TILs(P>0.05).2.Patients with IDO≥1 score are defined as positive,IDO is positive in 56 patients with TSCC(93.3%,56/60),and the positive rate is significantly correlated with postoperative treatment(X~2=13.089,P=0.004),it is not correlated with gender(X~2=0.917,P=0.338),age(X~2=0.262,P=0.609),lymph node metastasis(X~2=0.044,P=0.835),surgical resection margin status(X~2=0.033,P=0.856),tumor size(X~2=0.677,P=0.411),Masaoka-Koga stage(X~2=3.389,P=0.304),and preoperative treatment(P=1.0);in addition,intratumoral CD20(X~2=5.432,P=0.02)and CD68(X~2=6.735,P=0.009)positive cells infiltration are positively correlated;other TILs are not associated(P>0.05).3.PD-L1 and IDO are co-expressed in 42 cases of TSCC(70%,42/60),and there is a positive correlation between them(r=0.286,P=0.027).4.TILs infiltration is divided into high infiltration group and low infiltration group according to the median,CD4,CD20,CD21,FOXP3 in the stroma and CD4,CD8,CD20,CD21,CD56,FOXP3 in the tumor of high infiltration group and low infiltration group are negatively correlated with Masaoka-Koga stage(X~2=13.439,P=0.002;X~2=9.393,P=0.018;X~2=8.913,P=0.022;X~2=12.989,P=0.003;X~2=16.795,P=0.0001;X~2=10.69,P=0.009;X~2=12.792,P=0.003;X~2=9.463,P=0.018;X~2=7.414,P=0.038;X~2=12.654,P=0.003);CD4,CD8,CD20,FOXP3 in the stroma and CD20,CD56,FOXP3 in the tumor of high infiltration group and low infiltration group are significantly correlated with surgical resection margin status(X~2=7.33,P=0.007;X~2=4.689,P=0.03;X~2=5.714,P=0.017;X~2=5.006,P=0.025;X~2=5.714,P=0.017;X~2=4.49,P=0.034;X~2=5.714,P=0.017);CD4,CD8,CD20,CD21,FOXP3 in stroma and CD4,CD8,CD20,CD21,CD56,FOXP3 in tumor of high infiltrate and low infiltrate groups were significantly associated with germinal centers(X~2=22.0,P=0.001;X~2=10.34,P=0.001;X~2=13.13,P=0.001;X~2=49.10,P=0.001;2=4.286,P=0.038;X~2=17.14,P=0.001;X~2=9.32,P=0.002;X~2=24.10,P=0.001;X~2=27.81,P=0.001;X~2=5.46,P=0.020;X~2=9.64,P=0.002);there is no correlation between the other parameters(P>0.05).5.PD-L1(HR=0.230,P=0.007),IDO(HR=4.240,P=0.030)and germinal center formation(HR=0.282,P=0.010)are significantly associated with PFS in TSCC patients.Conclusion:1.PD-L1 is highly expressed in TSCC tissues;it is positively correlated with tumor size,Masaoka-Koga stage,stromal and intratumoral CD20~+B cells infiltration;2.IDO is highly expressed in TSCC tissues,and is positively correlated with CD20~+B cells and CD68+macrophages infiltration in tumors,but not with clinicopathologic features;3.The co-expression rate of PD-L1 and IDO in TSCC is high,and their expression is positively correlated,suggesting that PD-L1 and IDO may be synergistically involved in the occurrence,progression and metastasis of TSCC,and inhibiting their expression may block the occurrence and development of tumors.The combined detection of PD-L1 and IDO may provide a new way for the clinical treatment of TSCC;4.High PD-L1 expression,low IDO expression and germinal center formation are independent protective factors for PFS in TSCC patients.