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ASCO GI 2023 | Mechanisms of immune evasion in pancreatic cancer and what strategies to enhance immunotherapies

Kim Anna Reiss, MD, University of Pennsylvania, Philadelphia, PA, talks on mechanisms of immune evasion in pancreatic cancer and strategies to enhance the efficacy of immunotherapies. Some key mechanisms of immune evasion in pancreatic cancer are related to the tumor immune microenvironment (TME) preventing T-cell infiltration and comprising of tumor resident macrophages, one type which suppresses the immune system, amongst other immunosuppressive components. The pancreas is a naturally anti-inflammatory organ, further contributing to the immunosuppression of the TME. Strategies to stimulate a proinflammatory response could include moving immunotherapies into earlier lines of treatment, as well as into the maintenance setting, as well as investigating the myeloid lineage in addition to T-cell therapies. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Gastrointestinal Cancers (GI) Symposium in San Francisco, CA.

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Transcript (edited for clarity)

Some of the mechanisms of evasion in pancreatic cancer have to do with the tumor microenvironment, pancreatic cancer, I like to say it is sort of shrink-wrapped in a stroma that is very much interacting with the tumor and is working very hard to suppress the tumor. It prevents T-cell infiltration. You also have tumor resident macrophages as specific, which are in two different phenotypes, and one phenotype actually promotes tumor, so suppresses the immune system further...

Some of the mechanisms of evasion in pancreatic cancer have to do with the tumor microenvironment, pancreatic cancer, I like to say it is sort of shrink-wrapped in a stroma that is very much interacting with the tumor and is working very hard to suppress the tumor. It prevents T-cell infiltration. You also have tumor resident macrophages as specific, which are in two different phenotypes, and one phenotype actually promotes tumor, so suppresses the immune system further. So the pancreas itself is also kind of as an organ, sort of an anti-inflammatory organ. So if you have ever had known anybody with pancreatitis, it is an incredibly nasty entity and it can be fatal and can be very, very, very painful and bad for the body. So the body, the pancreas itself is designed to be anti-inflammatory to prevent such a state. So there’s a lot that’s working against you. It’s the tumor, the tumor microenvironment, and the native pancreas cancer, sorry, the native pancreas itself trying to work against you. So there are different ways that we’re going to have to think about trying to thwart that. One is potentially to interact with the cancer and the human before the immune system is already completely fried. So moving immunotherapies earlier into therapy, and that’s where we’re trying to put therapies now. Vaccine trials, there are adjuvant vaccine trials, but also into the maintenance therapy where the immune system’s not burned out. And potentially there are certain tumors that are more immunologically fit, I would say, or the patient’s more immunologically fit where those therapies actually might have a dent. Finally, looking at the myeloid compartment, rather than just focusing on anti T-cell therapies, I think will be very important for the reasons that I suggested.

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