The Application Of Multiple Antigen Stimulating Cellular Therapy (MASCT) And ALBI Grade System In Hepatocellular Carcinoma

Part 1.Multiple Antigen Stimulating Cellular Therapy(MASCT)For Hepatocellular Carcinoma After Curative Treatment:A Retrospective StudyBackground&Aims:The prognosis of hepatocellular carcinoma(HCC)remains poor and available treatment options are limited.This retrospective study evaluated the efficacy of Multiple Antigen Stimulating Cell Therapy(MASCT)as an adjuvant therapy for the treatment of HCC after curative treatment?Methods:Patients who underwent HCC curative treatments were classified into two groups:the MASCT group,in which patients received MASCT treatment after curative treatment(n=47),and the control group,in which patients did not receive any treatment after curative treatment(n=99).Patients who received?5 courses of MASCT treatment before recurrence or death(n=26)were further stratified into a subgroup(multiple-course MASCT group)for analysis.The primary endpoint was overall survival(OS).The secondary endpoints were disease-free survival(DFS)and safety?Results:Kaplan-Meier analysis showed no statistically significant difference in OS between the MASCT group and the control group(P=0.132),nor in DFS(P=0.310)(median:36.17 vs.24.27 months).However,when comparing the multiple-course MASCT treated group to the control group,Kaplan-Meier analysis showed a significant difference in OS(P=0.011),but not in DFS(P=0.104)(median:47.10 vs.24.27 months).The overall incidences of treatment-related adverse events in the MASCT group and control group were 14.89%(7/47)and 19.19%(19/99),respectively.No MASCT treatment-related serious adverse events were reported.Conclusions:Although the MASCT group was not associated with significantly longer OS or DFS,the multiple-course MASCT group showed significantly improved overall survival after curative treatment,and the treatment procedures were well-tolerated.Multiple-course MASCT may therefore provide another choice for patients with HCC after curative treatment.Part 2.The Correlation Between Gene Characteristics And Immune Response Of Patients With Hepatocellular Carcinoma.Background:The occurrence of tumor is the gradual process of the accumulation of multilevel gene mutatione.The heterogeneity of tumor is one of the most important features of malignant tumor.In this study,we analysis the changes of immune cells against propeptide response in patients undergoing MASCT treatment.Then epitope prediction and immunological mutation has been analyzed after two generation sequencing with tumor tissues.And the results were compared.Methods:13 patients received MASCT after curative treatment of HCC were enrolled.Responses to tumor associated antigen peptides in PBMC were detected in W0,W16,W31 respectively.Next generation sequencing of 355 tumor associated gene mutation was detected in 10 tumor tissues.Phenotypic characteristics of HLA-I class molecules were analyzed and epitopes of TAA were predicted.The result was compared with ELISPOT.Results:10 in 13 patients have completed with two circles of MASCT,8 in 13 patients have completed with three circles.The ELISPOT was detected in W0,W16,W31.The results showed that the specific T cell responses against each antigen were detected in 11/13 patients,however,with individualized distinct patterns.The most immunogenic TAAs are surviving,RGS5 and CCDN1 for HCC.These results were diacordance with the prediction of TAAs in tumor tissues.At the end of follow-up,tumor recurrence occurred in 3 patients(P9,P11,P13).The mutation of HLA-I homozygous and IL7R.p166T were detected in these patients.Conclusion:MASCT elicits strong and dynamic immune responses against multiple tumor associated antigens specifically.However,the patterns were different with different patients.The mechanisms still need further investigation.Part 3.External Validation Of the ALBI Grade System In the Reallife Cohort Of Hepatocellular Carcinoma.Background:Hepatocellular carcinoma may be developed from a variety of liver diseases.The clinical value of the traditional Child-Pugh(C-P)classification in the liver cancer remains to be further improved.As a new grading standard of liver function,the ALBI grading system has been verified by many regions in the world,and it can be applied in the prognosis evaluation of HCC.However,the value of its application in the Chinese population remains to be further verified.Methods:To set up a retrospective,prospective,single center,observational clinical cohort of HCC has been constructed in our department.ALBI grading system was validated in this cohort.Results:In all 898 patients,799(89%)were male and 808 cases were infected with HBV infection(90%).According to the ALBI scoring system,277(30.85%)patients were in grade 1,573(63.81%)patients were in grade 2,48(5.35%)patients were in grade 3.The overall compliance rate with the C-P classification system is 56.6%.The AIC of ALBI and C-P were 6011 and 6017,respectively,and Harrel 's C index were 0.603 and 0.597,respectively.The two systems both showed good presentation in discrimination,calibration,homogeneity and monotonicity of gradients.The clinical efficacy of prognosis prediction are equal.Conclusions:The ALBI grading system offers a evidence-based,simple,objective,and discriminatory method of assessing liver function in HCC which has been extensively tested in an international setting.It can also available in Chinese HCC patients.In addition,it can avoid interobserver variation and will highlight distinct prognostic subgroups within C-P grade A.All these advantages may give important considerations in the clinical application.