Hot and cold pancreatic cancer tumors

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A research team from the Abramson Cancer Center (ACC) at the University of Pennsylvania School of Medicine found that whether a tumor is hot or cold is determined by information embedded in the cancer cells themselves. “Hot” tumors are often considered more sensitive to immunotherapy. In a new study published this week in Immunity, the researchers explored the role of “tumor heterogeneity”, namely the ability of tumor cells to move, replicate, metastasize and respond to treatment. These new findings can help oncologists more accurately tailor the unique tumor composition of patients.

Ben Stanger, a professor of gastroenterology and cell and developmental biology at the University of Pennsylvania Perelman School of Medicine, said that the degree to which T cells are attracted to tumors is regulated by the tumor-specific genes. In order for tumors to grow, they need to avoid attacks by the immune system. There are two ways: to develop into cold tumors, or hot tumors that can deplete T cells, effectively protecting tumor cells from damage to the patient’s immune system.

In this study, researchers found that whether a tumor is hot or cold determines whether it will respond to immunotherapy. Cold tumor cells produce a compound called CXCL1, which can instruct bone marrow cells to enter the tumor, keep T cells away from the tumor, and ultimately make the immunotherapy insensitive. In contrast, knocking out CXCL1 in cold tumors promotes T cell infiltration and sensitivity to immunotherapy.

The team generated a series of cell lines that mimic the characteristics of pancreatic tumors, including the types of immune cells they contain. In the future, these tumor cell lines can help further identify and optimize treatment for specific subtypes of patients with various tumor heterogeneity states.

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