Pancreatic cancer is a disease with high unmet clinical need.Pancreatic cancer is also characterised by an intense fibrotic stroma,which harbours many immune cells.Studies in both human and animal models have demonstr...Pancreatic cancer is a disease with high unmet clinical need.Pancreatic cancer is also characterised by an intense fibrotic stroma,which harbours many immune cells.Studies in both human and animal models have demonstrated that the immune system plays a crucial role in modulating tumour onset and progression.In human pancreatic ductal adenocarcinoma,high B-cell infiltration correlates with better patient survival.Hence,B cells have received recent interest in pancreatic cancer as potential therapeutic targets.However,the data on the role of B cells in murine models is unclear as it is dependent on the pancreatic cancer model used to study.Nevertheless,it appears that B cells do organise along with other immune cells such as a network of follicular dendritic cells(DCs),surrounded by T cells and DCs to form tertiary lymphoid structures(TLS).TLS are increasingly recognised as sites for antigen presentation,T-cell activation,Bcell maturation and differentiation in plasma cells.In this review we dissect the role of B cells and provide directions for future studies to harness the role of B cells in treatment of human pancreatic cancer.展开更多
Pancreatic cancer remains one of medicine’s largest areas of unmet need.With five-year survival rates of<8%,little improvement has been made in the last 50 years.Typically presenting with advance stage disease,tre...Pancreatic cancer remains one of medicine’s largest areas of unmet need.With five-year survival rates of<8%,little improvement has been made in the last 50 years.Typically presenting with advance stage disease,treatment options are limited.To date,surgery remains the only potentially curative option,however,with such late disease presentation,the majority of patients are unresectable.Thus,new therapeutic options and a greater understanding of the complex stromal interactions within the tumour microenvironment are sorely needed to revise the dismal outlook for pancreatic cancer patients.Natural killer(NK)cells are crucial effector units in cancer immunosurveillance.Often used as a prognostic biomarker in a range of malignancies,NK cells have received much attention as an attractive target for immunotherapies,both as cell therapy and as a pharmaceutical target.Despite this interest,the role of NK cells in pancreatic cancer remains poorly defined.Nevertheless,increasing evidence of the importance of NK cells in this dismal prognosis disease is beginning to come to light.Here,we review the role of NK cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of NK cells as therapy.展开更多
基金Supported by Francesca Romana Delvecchio is supported by Cancer Research UK Post-doctoral fellowshipMichelle Goulart is supported by PCRF post-doctoral fellowshipRachel Elizabeth Ann Fincham is supported by PhD studentship awarded by Barts Charity(London,UK)and A^(*)STAR(Singapore)。
文摘Pancreatic cancer is a disease with high unmet clinical need.Pancreatic cancer is also characterised by an intense fibrotic stroma,which harbours many immune cells.Studies in both human and animal models have demonstrated that the immune system plays a crucial role in modulating tumour onset and progression.In human pancreatic ductal adenocarcinoma,high B-cell infiltration correlates with better patient survival.Hence,B cells have received recent interest in pancreatic cancer as potential therapeutic targets.However,the data on the role of B cells in murine models is unclear as it is dependent on the pancreatic cancer model used to study.Nevertheless,it appears that B cells do organise along with other immune cells such as a network of follicular dendritic cells(DCs),surrounded by T cells and DCs to form tertiary lymphoid structures(TLS).TLS are increasingly recognised as sites for antigen presentation,T-cell activation,Bcell maturation and differentiation in plasma cells.In this review we dissect the role of B cells and provide directions for future studies to harness the role of B cells in treatment of human pancreatic cancer.
基金Supported by the PhD Studentship Awarded by Barts Charity(London,United Kingdom)and A*STAR(Singapore)the Cancer Research UK Post-doctoral Fellowshipand the PCRF Postdoctoral Fellowship.
文摘Pancreatic cancer remains one of medicine’s largest areas of unmet need.With five-year survival rates of<8%,little improvement has been made in the last 50 years.Typically presenting with advance stage disease,treatment options are limited.To date,surgery remains the only potentially curative option,however,with such late disease presentation,the majority of patients are unresectable.Thus,new therapeutic options and a greater understanding of the complex stromal interactions within the tumour microenvironment are sorely needed to revise the dismal outlook for pancreatic cancer patients.Natural killer(NK)cells are crucial effector units in cancer immunosurveillance.Often used as a prognostic biomarker in a range of malignancies,NK cells have received much attention as an attractive target for immunotherapies,both as cell therapy and as a pharmaceutical target.Despite this interest,the role of NK cells in pancreatic cancer remains poorly defined.Nevertheless,increasing evidence of the importance of NK cells in this dismal prognosis disease is beginning to come to light.Here,we review the role of NK cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of NK cells as therapy.