Abstract
Pancreatic cancer is refractory to most current treatment options. Immunotherapy emerges as an effective and novel therapeutic strategy for several solid tumors. However, most of the clinical trials on immunotherapy have failed in pancreatic cancer. Understanding the underlying mechanism that drives immune evasion of pancreatic cancer is critical for overcoming resistance to therapy. Recently, Dr. He Ren and colleagues proposed a novel concept that a subset of epithelial cells in pancreatic cancer mimics the phenotype and function of regulatory T cells, named as “quasi-regulatory T cells.” These cells contribute to enhanced immune evasion, angiogenesis, and metastasis of pancreatic cancer, thus providing potential therapeutic targets to improve the sensitivity of immunotherapy for this devastating disease. This ground-breaking concept will advance our understanding on the immune evasion of pancreatic cancer and chart novel paths towards the development of personalized treatment for pancreatic cancer.
Highlights
Pancreatic adenocarcinoma (PDAC) remains the most lethal cancer with an overall 5-year survival rate of 10%
The present study provides a rationale for the combination of PD-L1 and CCL5 inhibition to improve the response to immunotherapy in PDAC, especially in patients with high c-FOXP3 levels
First of all, during the development of pancreatic cancer, what is the master regulator that controls the formation of “quasi-regulatory T cells”? Secondly, how to identify the biological effect of “quasi-regulatory T cells” during pancreatic tumorigenesis? Last but not the least, what is the difference between the transcriptomic networks of quasi-regulatory T cells and regulatory T cells in the same PDAC tissue? Through further investigation of those questions, we should be able to better understand the biology of PDAC, especially on immune evasion, and develop novel therapeutic targets to improve the effectiveness of immunotherapy in PDAC
Summary
Pancreatic adenocarcinoma (PDAC) remains the most lethal cancer with an overall 5-year survival rate of 10%. Little attention has been paid to the role of intrinsic factors derived from malignant epithelial cells in driving immune evasion. Epithelial cells mimic regulatory T cells in PDAC Dr He Ren and colleagues have recently published a series of papers focusing on understanding the role of immune regulatory factors derived from malignant epithelial cells [2,3,4,5,6,7].
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