Tumour microenvironment of pancreatic cancer: immune landscape is dictated by molecular and histopathological features

Abstract

Pancreatic cancer is a lethal disease, with fewer than 7% of patients surviving beyond 5 years following diagnosis. Immune responses are known to influence tumour progression. The dynamic interaction between cancer cells and immune cells in the tumour microenvironment (TME) can not only result in, or be influenced by, different tumour characteristics, but it can also lead to diverse mechanisms of immune evasion. At present, there is much interest in classifying pancreatic cancer according to its morphologic, genetic and immunologic features in order to understand the significant heterogeneity of this tumour type. Such information can contribute to the identification of highly needed novel prognostic and predictive biomarkers, and can be used for accurate patient stratification and therapy guidance. This review focuses on the characteristics of the local immune contexture of pancreatic ductal adenocarcinoma and the interaction between tumour cells and immune cells within the TME, by simultaneously taking into account the histomorphologic and genetic features of the tumours. The emerging opportunities for approaches that could predict the most-effective therapeutic modalities towards more targeted, personalised treatments to improve patient care are also discussed.

Single-nucleus and spatial transcriptomics of archival pancreatic cancer reveals multi-compartment reprogramming after neoadjuvant treatment

“…Despite substantial inter-tumor heterogeneity ( Figures 1C, S1 Figures S5A-B). One possibility is that these are driven through the effects of p63, especially the ΔNp63 isoform, though this remains an area of controversy in the field (11,89,90).…”

MYC Instructs and Maintains Pancreatic Adenocarcinoma Phenotype

“…Frank PDAC is characterized by its striking fibroinflammatory stroma, absent from normal pancreas, whose attendant dense desmoplasia typically constitutes some 90% of tumor bulk (5,6). This fibroinflammatory stroma is a product of complex interplay between tumor cells and adjacent mesenchymal, endothelial, inflammatory and immune cells and is thought to contribute to PDAC therapeutic recalcitrance by impeding vascular perfusion and oxygenation (7,8), and suppressing anti-tumor immunity (9).…”

Complete Response of Synchronous Liver Metastasis in a Pancreatic Ductal Adenocarcinoma: Could Surgery Represent a Therapeutic Option?

“…Both distant metastases [26][27] nodal involvement [28][29] and drug resistance [30][31][32] have been correlated with peculiar molecular signatures in PDAC. Cancer omics and biological signatures are able to stratify tumors depending on the cancer cell phenotype and the tumor niche, able to educate a neoplastic-friendly microenvironment for both solid and hematological cancer [33][34][35][36][37]. Resolving the spatial and clonal cancer heterogeneity, might provide fundamental clues able to deeper characterize translational target and oncogenic drivers, providing novel theragnostic targets.…”