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A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
The Tango between Cancer-Associated Fibroblasts (CAFs) and Immune Cells in Affecting Immunotherapy Efficacy in
Imke Stouten1, Nadine van Montfoort1, Lukas J A C Hawinkels1
1Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Abstract:
The lack of response to therapy in pancreatic ductal adenocarcinoma (PDAC) patients has contributed to PDAC having one of the lowest survival rates of all cancer types. The poor survival of PDAC patients urges the exploration of novel treatment strategies. Immunotherapy has shown promising results in several other cancer types, but it is still ineffective in PDAC. What sets PDAC apart from other cancer types is its tumour microenvironment (TME) with desmoplasia and low immune infiltration and activity. The most abundant cell type in the TME, cancer-associated fibroblasts (CAFs), could be instrumental in why low immunotherapy responses are observed. CAF heterogeneity and interactions with components of the TME is an emerging field of research, where many paths are to be explored. Understanding CAF-immune cell interactions in the TME might pave the way to optimize immunotherapy efficacy for PDAC and related cancers with stromal abundance. In this review, we discuss recent discoveries on the functions and interactions of CAFs and how targeting CAFs might improve immunotherapy.
Insights
Pancreatic cancer (PDAC) shows poor immunotherapy response due to its tumor microenvironment (TME). Targeting cancer-associated fibroblasts (CAFs) within the TME may enhance treatment efficacy for PDAC patients.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) exhibits dismal survival rates, largely due to therapeutic resistance.
- Immunotherapy, successful in other cancers, is largely ineffective in PDAC.
- The PDAC tumor microenvironment (TME), characterized by desmoplasia and immune suppression, hinders treatment efficacy.
Purpose of the Study:
- To review the role of cancer-associated fibroblasts (CAFs) in the PDAC TME.
- To explore CAF heterogeneity and their interactions with immune cells.
- To discuss the potential of targeting CAFs to improve immunotherapy in PDAC.
Main Methods:
- Literature review of recent discoveries on CAFs in PDAC.
- Analysis of CAF functions and interactions within the TME.
- Synthesis of current understanding of CAF-immune cell crosstalk.
Main Results:
- CAFs are a major cellular component of the PDAC TME.
- CAF heterogeneity influences the TME's immune-suppressive properties.
- CAF-immune cell interactions are critical determinants of immunotherapy response.
Conclusions:
- Understanding CAF biology and their TME interactions is crucial for PDAC treatment.
- Targeting CAFs presents a promising strategy to overcome immunotherapy resistance in PDAC.
- Further research into CAF-immune cell dynamics could optimize cancer therapies.
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