| Objective:Differentiated thyroid cancer is a common,low-grade endocrine tumor.The current treatments for DTC include surgery,endocrine therapy and radioactive iodine(1311)therapy.With the progression of disease,other methods such as radiation therapy and targeted therapy need to be applied when necessary.Immunotherapy is a rapid development in the treatment of tumors in recent years.It has achieved excellent results in many malignant tumors,but related research in differentiated thyroid cancer is still lacking.In our study,we will explore the expression of IDO-1,LAG-3,and TIM-3,which play an important role in tumor immunity,in DTC and their prognostic significance,and explore the possibility of its application in DTC immunotherapy.Among them,131I therapy is an effective treatment for patients with gross extrathyroidal extension(gETE).It is generally believed that 131I therapy can eliminate the small residual lesions that may exist after surgery and achieve the role of adjuvant therapy.However,it is still difficult to confirm the presence of small residual lesions or residual thyroid gland by imaging methods.Our study intends to explore the predictive value of the efficacy of SPECT/CT imaging in 131I adjuvant therapy.Materials and Methods:We first collected 119 patients with DTC who underwent surgical treatment in our hospital from 2014 to 2015.We stained the tissue specimen,recorded the expressions of IDO-1,LAG-3,and TIM-3 in the specimens and analyzed their correlation with the clinical characteristics and pathological indicators of corresponding patients.At the same time,the patients were followed up for 5 years,and the progression-free survival rate and its relationship with the expression of the above three immune checkpoints were statistically analyzed.Then we collected 88 patients with DTC who were treated with 131-I at Shanghai Sixth People's Hospital from the end of 2017 to mid-2019.These patients were found to have gross extrathyroidal extension during surgery.Statistical analysis was performed on the serological parameters and SPECT/CT results after the first 1311 treatment of these patients,and the thyroid function indicators of the patients after 6 months of follow-up.Results:In the part of the immune checkpoint,the positive rates of LAG-3 and TIM-3 in cancer tissues were 21.85%and 78.15%respectively,which were significantly higher than those of normal thyroid tissues.While the positive rate of IDO-1 was 78.15%,which did not show a significantly different from that in normal thyroid tissues.Factors associated with the high expression of LAG-3 included tumors with a single lesion(P=0.010).A 5-year-follow-up found that the overall 5-year progression-free survival rate for the entire cohort was 76.47%.Among patients with relapse or metastasis,55.56%found positive expression of LAG-3.Log-rank test(P=0.026)and multivariate Cox regression analysis(P=0.046)suggested that LAG-3 positive expression is an independent risk factor of progression-free survival.The same analysis of TIM-3 found no clinicopathological factors related to TIM-3 high expression and found no association between TIM-3 high expression and DTC recurrence or metastasis.In the part of adjuvant treatment,after the first 1311 treatment of gETE patients,there was no significant correlation between the iodine uptake on the ipsilateral side of gross extrathyroidal extension and the clinical pathological factors of the patients.However,the Tg level was significantly higher in the patients who had iodine uptake on the ipsilateral side both before and after treatment than in patients without ipsilateral iodine(P=0.026?P=0.037).Conclusion:The expression of LAG-3 and TIM-3 in immune checkpoints was significantly increased in differentiated thyroid cancer tissues,and the high expression of LAG-3 was associated with worse prognosis,suggesting that LAG-3 may be a potential target for immunotherapy of differentiated thyroid cancer point.For those patients with differentiated thyroid cancer with gETE whose 131I-SPECT/CT imaging revealed localized invasion of the ipsilateral foci on the ipsilateral side,Tg levels were higher before and after treatment,suggesting that there may be residual thyroid or Residual lesions may have a relatively poor prognosis. |
PDF Full Text Request