MHCII+ cancer-associated fibroblasts promote antitumor immunity in pancreatic cancer
The functions of major histocompatibility complex class II molecule-expressing cancer-associated fibroblasts (MHCII+CAFs) in pancreatic cancer remain controversial. MHCII+CAFs are primarily described as immunosuppressive, as MHCII allows for direct interaction with, and support of, regulatory T cells (Tregs). However, MHCII+CAF functions may be more complex depending on their origins and their…
Pancreatic cancer has long been associated with the role of cancer-associated fibroblasts (CAFs) expressing the major histocompatibility complex class II molecule (MHCII). Traditionally, MHCII+CAFs have been considered immunosuppressive due to their ability to interact with and support regulatory T cells (Tregs). However, the complexity of MHCII+CAFs' functions within the tumor microenvironment has been revealed through recent research using orthotopic models.
The study shows that conventional CD4+ T cells, and their production of Interferon gamma (IFN{gamma}), can increase the presence of MHCII+CAFs in pancreatic cancer tumors. When Tregs were depleted using Foxp3DTR mice, it was discovered that Tregs suppress the abundance of MHCII+CAFs in tumors. This inhibition is achieved by interfering with CD4 T cell responses that directly control primary tumor growth and metastatic progression.
Crucially, MHCII expression on fibroblasts proved to be essential for the control of PDAC (pancreatic ductal adenocarcinoma) progression when Tregs were removed. These findings identify an IFN{gamma}-driven, antitumor activity of MHCII expression on CAFs. The study further suggests that CAFs can be leveraged to promote adaptive immunity against pancreatic cancer.
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