Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer

Xinglong Geng; Hongze Chen; Liang Zhao; Jisheng Hu; Wenbo Yang; Guanqun Li; Chundong Cheng; Zhongjie Zhao; Tao Zhang; Le Li; Bei Sun

doi:10.3389/fcell.2021.655152

Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer

Front Cell Dev Biol. 2021 Jul 15:9:655152. doi: 10.3389/fcell.2021.655152. eCollection 2021.

Authors

Xinglong Geng^{1

2

3}, Hongze Chen^{1

2}, Liang Zhao⁴, Jisheng Hu^{1

2}, Wenbo Yang^{1

2}, Guanqun Li^{1

2}, Chundong Cheng^{1

2}, Zhongjie Zhao^{1

2}, Tao Zhang^{1

2}, Le Li^{1

2}, Bei Sun^{1

2}

Affiliations

¹ Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
² Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
³ Department of Abdominal Endoscopic Surgery, Affiliated Hospital of Qinghai University, Xining, China.
⁴ Department of Gynecology, Qinghai University Affiliated Hospital, Xining, China.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that typically features a dramatic desmoplastic reaction, especially fibroblasts. The roles of cancer-associated fibroblasts (CAFs) in PDAC have received more attention in recent years. As increasing evidence suggests the heterogeneity of CAFs in PDAC, different CAF subtypes have been shown to support tumor growth, while others suppress cancer proliferation. Myofibrotic CAFs (myCAFs) show alpha-smooth muscle actin (α-SMA) ^high interleukin-6 (IL-6) ^low myofibroblastic features, are activated by direct contact with tumor cells, and are located in the periglandular region. Inflammatory CAFs (iCAFs) show α-SMA ^low IL-6 ^high inflammatory features, are activated by paracrine factors secreted from tumor cells, and are located away from cancer cells. Antigen-presenting CAFs (apCAFs) show major histocompatibility complex II (MHC II) family genes that are highly expressed. CAFs have also been gradually explored as diagnostic and prognostic markers in pancreatic cancer. Targeted therapy of CAFs in PDAC has gradually attracted attention. With the deepening of related studies, some meaningful positive and negative results have surfaced, and CAFs may be the key to unlocking the door to pancreatic cancer treatment. Our review summarizes recent advances in the heterogeneity, function, and markers of CAFs in pancreatic cancer, as well as research and treatment targeting CAFs in pancreatic cancer.

Keywords: cancer-associated fibroblasts; diagnosis; hallmark; heterogeneity; pancreatic cancer; prognosis; therapy.

Publication types

Review