Hepatocellular carcinoma(HCC)is an aggressive primary liver neoplasm that,according to tumor stage,can be treated with resection,transplantation,locoregional treatment options,or systemic therapy.Although intervention...Hepatocellular carcinoma(HCC)is an aggressive primary liver neoplasm that,according to tumor stage,can be treated with resection,transplantation,locoregional treatment options,or systemic therapy.Although interventions only in early-stage disease can offer complete tumor regression,systemic therapy in advanced disease can significantly prolong overall survival,according to published clinical trials.The emergence of immunotherapy in the field of cancer therapy has had a positive impact on patients with HCC,resulting in atezolizumab–bevacizumab currently being the first-line option for treatment of advanced HCC.In light of this,application of immunotherapy in the preoperative process could increase the number of patients fulfilling the criteria for liver transplantation(LT).Implementation of this approach is faced with challenges regarding the safety of immunotherapy and the possibly increased risk of rejection in the perioperative period.Case reports and clinical trials assessing the safety profile and effectiveness of neoadjuvant immunotherapy,highlight important aspects regarding this newly evolving approach to HCC management.More studies need to be conducted in order to reach a consensus regarding the optimal way to administer immunotherapy prior to LT.In this review,we summarize the role,safety profile and future considerations regarding the use of neoadjuvant immunotherapy prior to LT in patients with HCC.展开更多
BACKGROUND Chronic kidney disease is associated with immunological disorders,presented as phenotypic alterations of T lymphocytes.These changes are expected to be restored after a successful renal transplantation;howe...BACKGROUND Chronic kidney disease is associated with immunological disorders,presented as phenotypic alterations of T lymphocytes.These changes are expected to be restored after a successful renal transplantation;however,additional parameters may contribute to this process.AIM To evaluate the impact of positive panel reactive antibodies(PRAs)on the restoration of T cell phenotype,after renal transplantation.METHODS CD4CD28null,CD8CD28null,natural killer cells(NKs),and regulatory T cells(Tregs)were estimated by flow cytometry at T0,T3,and T6 which were the time of transplantation,and 3-and 6-mo follow-up,respectively.Changes were estimated regarding the presence or absence of PRAs.RESULTS Patients were classified in two groups:PRA(-)(n=43)and PRA(+)(n=28)groups.Lymphocyte and their subtypes were similar between the two groups at T0,whereas their percentage was increased at T3 in PRA(-)compared to PRA(+)[23(10.9-47.9)vs 16.4(7.5-36.8)μ/L,respectively;P=0.03].Lymphocyte changes in PRA(-)patients included a significant increase in CD4 cells(P<0.0001),CD8 cells(P<0.0001),and Tregs(P<0.0001),and a reduction of NKs(P<0.0001).PRA(+)patients showed an increase in CD4(P=0.008)and CD8(P=0.0001),and a reduction in NKs(P=0.07).CD4CD28null and CD8CD28null cells,although initially reduced in both groups,were stabilized thereafter.CONCLUSION Our study described important differences in the immune response between PRA(+)and PRA(-)patients with changes in lymphocytes and lymphocyte subpopulations.PRA(+)patients seemed to have a worse immune profile after 6 mo follow-up,regardless of renal function.展开更多
文摘Hepatocellular carcinoma(HCC)is an aggressive primary liver neoplasm that,according to tumor stage,can be treated with resection,transplantation,locoregional treatment options,or systemic therapy.Although interventions only in early-stage disease can offer complete tumor regression,systemic therapy in advanced disease can significantly prolong overall survival,according to published clinical trials.The emergence of immunotherapy in the field of cancer therapy has had a positive impact on patients with HCC,resulting in atezolizumab–bevacizumab currently being the first-line option for treatment of advanced HCC.In light of this,application of immunotherapy in the preoperative process could increase the number of patients fulfilling the criteria for liver transplantation(LT).Implementation of this approach is faced with challenges regarding the safety of immunotherapy and the possibly increased risk of rejection in the perioperative period.Case reports and clinical trials assessing the safety profile and effectiveness of neoadjuvant immunotherapy,highlight important aspects regarding this newly evolving approach to HCC management.More studies need to be conducted in order to reach a consensus regarding the optimal way to administer immunotherapy prior to LT.In this review,we summarize the role,safety profile and future considerations regarding the use of neoadjuvant immunotherapy prior to LT in patients with HCC.
文摘BACKGROUND Chronic kidney disease is associated with immunological disorders,presented as phenotypic alterations of T lymphocytes.These changes are expected to be restored after a successful renal transplantation;however,additional parameters may contribute to this process.AIM To evaluate the impact of positive panel reactive antibodies(PRAs)on the restoration of T cell phenotype,after renal transplantation.METHODS CD4CD28null,CD8CD28null,natural killer cells(NKs),and regulatory T cells(Tregs)were estimated by flow cytometry at T0,T3,and T6 which were the time of transplantation,and 3-and 6-mo follow-up,respectively.Changes were estimated regarding the presence or absence of PRAs.RESULTS Patients were classified in two groups:PRA(-)(n=43)and PRA(+)(n=28)groups.Lymphocyte and their subtypes were similar between the two groups at T0,whereas their percentage was increased at T3 in PRA(-)compared to PRA(+)[23(10.9-47.9)vs 16.4(7.5-36.8)μ/L,respectively;P=0.03].Lymphocyte changes in PRA(-)patients included a significant increase in CD4 cells(P<0.0001),CD8 cells(P<0.0001),and Tregs(P<0.0001),and a reduction of NKs(P<0.0001).PRA(+)patients showed an increase in CD4(P=0.008)and CD8(P=0.0001),and a reduction in NKs(P=0.07).CD4CD28null and CD8CD28null cells,although initially reduced in both groups,were stabilized thereafter.CONCLUSION Our study described important differences in the immune response between PRA(+)and PRA(-)patients with changes in lymphocytes and lymphocyte subpopulations.PRA(+)patients seemed to have a worse immune profile after 6 mo follow-up,regardless of renal function.
