Meta-analysis Of The Relationship Between Tumor Infiltrating Lymphocytes And Prognosis Of Malignant Melanoma

Objectives:The incidence of malignant melanoma increases year by year,and the mortality rate is high.There is no ideal treatment plan.More and more studies have found that malignant melanoma is sensitive to the tumor infiltrating lymphocyte treatment,but as a new treatment method,TIL therapy remains controversial in its effectiveness on patients' prognosis.This study aims to fully investigate and evaluate the effect of TIL therapy on the prognosis of patients with malignant melanoma by using meta-analysis(MA)and systematic reviews.Methods:Computer search of PubMed,EMBASE,Sino Med,Springer,Science Direct,The Cochrane Liabray,and Web of Science databases,etc.,Chinese Knowledge Base(CNKI),Chinese Biomedical Literature Database(CBM),Wanfang Medical Network,CQVIP Database,meanwhile,the relevant references in the literature are also included to avoid omissions.The cut off date for searching is December 31,2017.English searching keywords are:"tumor infiltrating lymphocyte","TIL","lymphocyte","melanoman";Chinese searching keywords:"tumor infiltrating lymphocytes","malignant melanoma." Literature searched by combining the subject headings with entry terms,and incorporate reference materials published in Chinese or English.The Meta analysis was performed using Rev Man 5.1,STATA sofeware version 11.2 software.The relative hazard ratio(HR)and 95%confidence interval(CI)values were calculated and used to examine the risk association of the study.Results:A total of 19 articles were included,the meta-analysis of the data on 14006 patients with malignant melanoma showed that:the overall survival(OS)of TIL treatment and malignant melanoma(HR=0.50,95%CI(0.40-0.64),p<0.001)and disease-free survival(DFS/progression-free survival(PFS)(HR=0.57,95%CI(0.49-0.67),p<0.001).The results are statistically significant,suggesting that patients with malignant melanoma can benefit from TIL therapy.Further subgroup analysis of the effects of TIL therapy combined with conventional treatment with interleukin-2(IL-2)and the use of IL-2 alone on the overall survival of patients was statistically significant(HR=0.56,95%CI(0.33-0.95),p=0.032),confirming that TIL+IL-2 treatment and conventional IL-2 treatment can significantly improve the prognosis of patients;another subgroup analysis of TIL treatment for malignant melanoma with lymph node metastasis.The effect of OS in the patient was not statistically significant(HR=0.74,95%CI 0.54-1.01)p=0.056),suggesting that TIL treatment did not significantly improve the prognosis of patients with malignant melanoma with lymph node metastasis.In addition,the subgroup analysis of TIL treatment of stage III malignant melanoma patients with OS,the results were statistically significant(HR =0.51,95%CI(0.27-0.96),p = 0.036),suggesting that TIL treatment can extend the the overall survival rate of patients with stage III malignant melanoma.Conclusions:1.TIL treatment is significantly associated with the prognosis of patients with malignant melanoma,TIL treatment can prolong the overall survival rate and disease-free survival/progression-free survival rate of patients with malignant melanoma;2.TIL treatment based on traditional treatment IL-2 can significantly prolong the patient's life Duration;3.TIL treatment of malignant melanoma in patients with the prognosis and whether there is no significant phase of lymph node metastasis relevance;4.TIL treatament can improve the survival rate of patients with stage III malignant melanoma,suggesting that the prognosis of patients with advanced melanoma can benefit from TIL therapy.