Prognostic Significance Of CD3+CD8+Tumor-Infiltrating Lymphocyte(TILs) And Programmed Cell Death 1 Ligand 1(PD-L1)Expression In Papillary Thyroid Carcinoma

BackgroundPapillary thyroid carcinoma,accounting for about 90%of thyroid carcinoma,is usually curable with surgery,radioactive iodine(RAI),and thyroid-stimulating hormone(TSH)suppression.However,local recurrence and/or distant metastases occur in approximately 25%of cases during follow-up,and nearly two-thirds of these patients will become RAI?refractory DTC(RR-DTC)with a poor prognosis.Co-signaling molecular programmed cell death 1 ligand 1(PD-L1)has been shown to effectively inhibit T cell-mediated anti-tumor immunity.Tumor infiltrating lymphocytes have been shown to be associated with prognosis.In colorectal cancer,someone have developed a prognostic score("Immunoscore")that takes into account the distribution of the density of both CD3?lymphocytes and CD8+cytotoxic T cells in the tumor core and the invasive margin that could outperform TNM staging.ObjectivesWe detected the expression of programmed cell death 1 ligand 1 and CD3+CD8?tumor infiltrating lymphocytes in papillary thyroid carcinoma to explore the value of PD-L1 expression and CD3+CD8+TILs-based "Immunoscore" in the prognosis of papillary thyroid carcinoma.MethodsThe clinical data and histopathological specimens of 34 patients with PTC treated and followed up in our hospital were analyzed retrospectively,including age,sex,tumor size,multifocal,capsular marginal state,pT stage,pN stage,disease recurrence and survival data.By immunohistochemistry of CD3 CD8 and PD-L1 in wax tissue,the stained cells were counted manually and analyzed for clinical and histopathologic correlations and disease-free survival.ResultsPatients with low CD8?and CD3+expression in tumor presented with a significantly higher incidence of extrathyroidal extension(p=0.012)and lymph node metastasis(p<0.001).Tumor infiltrating lymphocyte density was significantly correlated with tumor size(p=0.019)and multiplicity(p=0.03).Univariate analysis showed that the“Immunoseore,was significantly associated with differences in disease-free survival(hazard ratio[HR],13.250,2.077,and 84.522,respectively;p<0.001).A final stepwise model for Cox multivariate analysis supports the advantage of the "Immunoscore"(relative risk[RR],0.096;0.015,0.597;p=0.012)compared with histopathologic features in predicting recurrence.Regions receiver operating characteristic curve analysis was show that assessment of"Immunoscore"(AUC=0.954)provides an indicator of tumor recurrence beyond that predicted by AJCC TNM staging.All 34 patients with papillary thyroid earcinoma had negative programmed cell death 1 ligand 1 expression in tumors,only expressed in poorly differentiated regions,and the expression intensity was less than 10%.The expression of PD-L1 was positive in 2 of 5 cases of anaplastic thyroid carcinoma,and the expression intensity was higher and more frequent.ConclusionThe expression of CD3?CD8?tumor infiltrating lymphocytes can be used to identify more invasive PTC patients.The "IImmunoscore" based on the expression of CD3?CD8+T cells in specific tumor areas is a useful index to predict the recurrence of papillary thyroid carcinoma,and the predictive performance may better than the current traditional prediction parameters.PD-L1 may be of therapeutic significance in poorly differentiated thyroid carcinoma,but it is of little value in the prognosis of PTC.