Two cell types work together to protect pancreatic tumors from destruction by the immune system. But, blocking this partnership may restore the system鈥檚 ability to attack these same tumor cells.
These are the findings of a study of mice led by researchers from 嘿嘿视频 Health and its Perlmutter Cancer Center, and published online July 18 in Cell Reports.
The study results revolve around the immune system, which is designed to attack invaders like viruses. Immune cells also recognize cancer cells as abnormal, but such cells have the ability to turn off immune responses.
Pancreatic cancer cells, for instance, give off signaling molecules that attract regulatory T cells (Tregs), which lessen immune responses and create a 鈥渢olerance鈥 to cancer鈥檚 presence. The mechanisms behind this have not been clear.
The current study found that Tregs have their effect by keeping a second cell type, dendritic cells, from activating a third cell type, CD8+ T cells, which would otherwise kill cancer cells.
鈥淥ur results argue that blocking the partnership between Tregs and dendritic cells might be needed to achieve effective immunotherapy for pancreatic cancer,鈥 says lead author , vice dean for science and chief scientific officer at 嘿嘿视频. 鈥淯pcoming studies in our lab will be looking to confirm that this relationship can become the foundation of new treatment strategies.鈥
The study focused on pancreatic ductal adenocarcinoma (PDA), a lethal form of cancer known to come with an influx of immune cells into tumors. Past studies have linked the early Treg build-up in tumors with reduced survival.
As part of the normal immune response, T cells partner with dendritic cells to 鈥渄ecide鈥 which protein pieces of viruses or cancer cells will be used to grab the immune system鈥檚 attention. Upon encountering a cancer cell protein, a dendritic cell 鈥渟wallows it,鈥 breaks it up, and displays the pieces on its surface for notice by T cells in the nearest lymph node.
The research team suggests that this normal contact between the two cell types is exploited by cancer cells, in which contact-based, mutually reinforcing cross-talk between them turns off the immune response. The same results suggest the Tregs and killer T cells may in fact compete for dendritic cells near tumors, say the authors.
When antibodies and other methods were used to dramatically deplete the supply of Tregs in mice, the researchers saw a dramatic jump in the numbers of activated dendritic cells and CD8+ T cells in pancreatic tumor tissue, as well as a slowing of tumor growth.
Of note, the current study is part of a recent surge in 嘿嘿视频 findings on pancreatic cancer, including studies on how first-responder cells turn off the immune response, the role of the drug nab-paclitaxel in tumor biology, cancer cells鈥 unique fuel sources, and how immune cell infighting drives the disease. Along these lines, Perlmutter Cancer Center recently announced the creation of a multidisciplinary center of excellence to develop innovative approaches to diagnose, treat, and prevent pancreatic cancer.
Along with Dr. Bar-Sagi, the study was led by Michael Dustin of the Nuffield Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences at the University of Oxford. Also authors were Jung-Eun Jang in the Skirball Institute of Biomolecular Medicine, Cristina Hajdu of the Department of Pathology, and Caroline Liot in the Department of Biochemistry and Molecular Pharmacology, all within 嘿嘿视频.
The study was supported by Perlmutter Cancer Center grant P30CA016087; National Institutes of Health grants S10 RR023704, R01AI055037, CA210263; Wellcome Trust grant PRF 100262Z/12/Z; Stand Up To Cancer-Lustgarten Foundation grant SU2C-AACR-DT14-14; Project Purple; and a Zeiss LSM 710 grant to the at 嘿嘿视频 Health.
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