Cancer immunotherapy, which boosts the patient̵7;s immune system to eliminate tumors, is revolutionizing cancer treatment. Many patients respond well to these treatments, sometimes in long-term remission. But some cancers are still difficult to treat with immunotherapy, and expanding the impact of this approach is a top priority.
In the October 30 issue of Proceedings of the National Academy of Sciences, a group led by scientists Tobias Janowitz and Douglas Fearon of Cold Spring Harbor Laboratory along with Duncan Jodrell at the UK Cancer Research Center and Institute, University of Cambridge, reports on a clinical trial. screening of a drug that induces an integrated immune response in tumors in patients with other types of cancer that often do not respond to immunotherapy. Researchers hope potential treatments could make these tumors more responsive to a class of drugs known as immune control point inhibitors.
Checkpoint inhibitors release the natural immune system, releasing it to find and destroy cancer cells. But they are generally ineffective against cancer cells with low levels of genetic mutations. Janowitz says:
“These tumors don’t seem to be seen by the immune system and are unlikely to be exposed by these currently available therapies. And we have reason to believe that it is because they can participate. an immunosuppressive pathway that helps keep most of the immune cells out of the nest of cancer cells. “
In this clinical trial, the team disrupted that pathway of immunosuppression with a drug called plerixafor. The drug is administered intravenously continuously for a week to 24 patients with pancreatic cancer or colorectal cancer with a low tumor mutation burden. All patients had progressive disease, and biopsies were collected from tumors that metastasized before and after treatment.
When the team analyzed those samples, they discovered that vital immune cells had penetrated the tumors during the time the patient received plerixafor, including a type of cell known to convene and organize people to play a key role in anti-cancer responses. This finding is encouraging because the team found changes that were also observed in cancer patients who responded well to control point inhibitors.
Jodrell, who leads the planning and recruiting of patients for clinical research, said, “I am delighted that the work of this multidisciplinary team has translated important laboratory findings into patients, with the potential to make a difference in cancer treatments. “A clinical trial based on this research is about to begin, and will test the effects of combining plerixafor with a checkpoint inhibitor. control approved.
Signs can predict a patient’s response to cancer immunotherapy
Biasci, D., et al., “CXCR4 inhibition in pancreatic and colorectal cancers in humans inducing an integrated immune response”, PNAS, October 30, 2020. DOI: 10.1073 / pnas.2013644117
Provided by Cold Spring Harbor Laboratory
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