Penetrating the Shield of Scar-Like Cells That Protect Pancreatic Tumors

Penetrating the Shield of Scar-Like Cells That Protect Pancreatic Tumors ...

A new study by UTSouthwestern claims that scar-like tissues that complement malignant pancreatic tumors and shield them from immune damage are proven from mesothelial cells that line tissues and organs. Pancreatic cancer, a deadly disease, is believed to be a valuable component of these benign pancreatic tumors.

According to Dr. Huang, the group''s professor of surgical, therapy and in the Hamon Center for Therapeutic Oncology and a member of theHarold C. Simmons Comprehensive Cancer Center, we might someday be able to increase the effectiveness of immune therapy in pancreatic cancer patients.

According to the American Cancer Society, approximately 56,000 people in the United States are diagnosed each year with pancreatic ductal adenocarcinoma (PDA), the most common form of pancreatic cancer. Despite decades of research, the prognosis for PDA is still unclear, with only 10% of patients returning five years after diagnosis.

CAFs, which are similar to the fibroblasts that compose scar tissue, are dense and tough in pancreatic cancer, preventing chemotherapy or other therapies from reaching cancer cells. In an earlier study in 2019, Dr. Huang explained that these pancreatic CAFs had a distinct set of limitations. One of them is a subtype known as antigen-presenting CAFs, which enables antibodies to interact with their surface.

Dr. Huang, Dr. Brekken, and their colleagues used a technique known as lineage tracing to discover how these cells arise as a normal pancreas develop cancer. Their findings showed that apCAFs are produced by mesothelial cells, which form a protective membrane that lines organs, body cavities, and tissues.

Further experiments showed that the antigens on the surface of apCAFs might convert immune cells called T-cells into regulatory T-cells (Tregs), which protect tumors from immune attack. When researchers dosed mice carrying pancreatic tumors with antibodies against mesothelin, the conversion to Tregs was blocked, putting tumors more vulnerable to an anti-tumor immune response.

Although further research is required in animal models, Dr. Huang said that it may be possible to employ a similar approach to treat PDA in humans by administering anti-mesothelin antibodies in combination with immunotherapies that stimulate the immune system to treat cancers.

Dr. Brekken, an Effie Marie Cain Research Scholar, stated that the study clarifys the origin and function of apCAFs in PDA, although it has implications beyond pancreatic cancer, and that Dr. Huang will continue to investigate.

Yuqing Zhang, Debolina Ganguly, Raghav Chandra, Gilbert Murimwa, Steven Wright, Xiaowu Gu, and Ravikanth Maddipati are among those who contributed to this study.

The National Institutes of Health (K99 CA252009, R01 CA243577, and U54 CA210181 Project 2), the Effie Marie Cain Fellowship, and the Jean Shelby Fund for Cancer Research at the Communities Foundation of Texas.

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