T cells in pancreatic cancer stroma

Pancreatic ductal adenocarcinoma(PDAC)is a highly devastating disease with a dismal 5-year survival rate.PDAC has a complex tumour microenvironment;characterised by a robust desmoplastic stroma,extensive infiltration of immunesuppressive cells such as immature myeloid cells,tumour-associated macrophages,neutrophils and regulatory T cells,and the presence of exhausted and senescent T cells.The cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance,disease progression and spread to distant organs.PDAC tumours,considered to be non-immunogenic or cold,express low mutation burden,low infiltration of CD8+cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue,and often display an exhausted phenotype.Here,we review the role of T 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 T cells as therapy.

B cells in pancreatic cancer stroma

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.

Natural killer cells in pancreatic cancer stroma

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.