Metastasis-associated fibroblasts in peritoneal surface malignancies

Area of Science:

• Oncology
• Cancer Biology
• Peritoneal Malignancies

Background:

• Peritoneal surface malignancies (PSMs) historically had poor prognoses and limited treatments.
• Advancements in chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved outcomes.
• PSMs arise from intra-abdominal cancers, primarily colorectal, ovarian, and gastric, forming peritoneal metastases.

Purpose of the Study:

• To investigate the role of the peritoneal microenvironment in PSMs.
• To characterize the heterogeneity and origin of peritoneal metastasis-associated fibroblasts (MAFs).
• To understand how MAFs influence tumor progression and therapy resistance in PSMs.

Main Methods:

• Review of studies on peritoneal surface malignancies.
• Analysis of single-cell RNA sequencing data.
• Characterization of fibroblast subtypes within the peritoneal microenvironment.

Main Results:

• Peritoneal metastasis-associated fibroblasts (MAFs) are heterogeneous and play a crucial role in PSM development and therapy resistance.
• Immune-regulatory cancer-associated fibroblasts (iCAFs) are the most prevalent MAF subtype in PSMs.
• Other observed subtypes include myofibroblastic CAFs (myCAFs) and matrix CAFs (mCAFs).

Conclusions:

• Peritoneal MAFs exhibit plasticity and heterogeneity, originating from various cell types.
• Understanding the complex interactions within the PSM microenvironment is vital.
• Targeted therapies focusing on these interactions are crucial for improving patient outcomes in PSMs.