The Tumor Microenvironment in Pancreatic Cancer Flashcards
(15 cards)
What characterizes the histology of PDAC?
PDAC is characterized by a dense stromal matrix consisting of various cellular and acellular components.
What is the tumor microenvironment (TME) in pancreatic cancer?
The TME, also referred to as desmoplastic reaction, evolves early around PanIN lesions and makes up to 90% of the tumor bulk in frank carcinomas.
What are the predominant cell types within the TME of PDAC?
The predominant cell types are cancer-associated fibroblasts (CAFs), regulatory and cytotoxic immune cells, macrophages, neurons, and endothelial cells.
What is the composition of non-epithelial cells in PDAC tumors?
The majority of non-epithelial cells are myeloid cells, primarily macrophages and neutrophils, while CAFs make up approximately 2% of all cells.
How do human and mouse PDAC tumors differ in T and B lymphocyte proportions?
Mouse tumors show a lower proportion of T and B lymphocytes compared to human tumors, while myeloid cells are fairly evenly distributed.
What regulates T cell exclusion from murine PDAC?
T cell exclusion is regulated by granulocytes, fibroblasts, and tumor-associated macrophages (TAMs) within and outside the microenvironment.
What potential therapeutic strategies could enhance T cell immunotherapy in PDAC?
Therapeutic strategies to reinforce T cell influx in PDAC might enhance T cell immunotherapy.
What role do cells within the TME play?
Cells within the TME interact and produce large amounts of ECM components, growth factors, matricellular proteins, enzymes, and cytokines.
What is the impact of the complex interactions within the TME on therapeutic targeting?
The complex regulatory circuits in the TME make it impossible to predict biological behavior if a single pathway or molecule is targeted.
What recent advancements have been made in understanding the TME of PDAC?
Single-cell RNA and protein analytics have identified significant single-cell populations within the TME that determine tumor cell characteristics and clinical outcomes.
What historical view existed regarding the desmoplastic reaction in pancreatic cancer?
Historically, the desmoplastic reaction was seen as a defensive response to confine tumor growth and spread, similar to fibrotic reactions in chronic pancreatitis.
What evidence has emerged regarding the role of the TME in pancreatic tumorigenesis?
Numerous studies have shown that components of the TME promote pancreatic tumorigenesis.
What is the current status of anti-stromal therapies in pancreatic cancer?
Despite optimism, the majority of preclinical results have not been replicated in clinical trials, and there are currently no approved anti-stromal therapies.
What did recent data from GEMMs reveal about TME components?
Therapeutic depletion of TME components may result in more aggressive and metastatic pancreatic tumors, indicating some components may restrain tumors.
What is the aim of the review discussed in the text?
The review aims to illustrate different compartments of the TME in pancreatic cancer and explain biological, pathophysiological, and therapeutic concepts.
