Giving the immune system a double enhance in opposition to most cancers

A highly specialized cell, the fibroblastic reticular cell, coordinates the immune responses to cancer cells. In this image, a single fibroblastic reticular cell is identified by staining: the nucleus (blue), markers that identify fibroblast cells (red), and a molecule that attracts immune cells (green). Photo credit: CSHL, 2020

Cancer immunotherapies, which enable patients’ immune systems to eradicate tumors, are revolutionizing cancer treatment. Many patients respond well to these treatments and sometimes have long lasting remissions. However, some cancers continue to be difficult to treat with immunotherapy, and expanding the effectiveness of the approach is a high priority.

In the October 30 issue of the Proceedings of the National Academy of Sciences, a team led by scientists Tobias Janowitz and Douglas Fearon from the Cold Spring Harbor Laboratory together with Duncan Jodrell from the Cambridge Institute and Center of Cancer Research UK reported on a clinical trial trial a drug that induces an integrated immune response in the tumors of patients with cancers that normally do not respond to immunotherapy. The researchers hope that the potential treatment could result in such tumors responding better to the class of drugs known as immune checkpoint inhibitors.

Checkpoint inhibitors release and release natural brakes on the immune system to find and destroy cancer cells. However, they were generally not effective against cancer cells with low genetic mutations. Janowitz said:

“These tumors often appear not to be visible to the immune system and are not exposed by these currently available therapies. We have reason to believe that this is because they can take an immunosuppressive pathway that sustains most of it.” the immune cells from the cancer cell nest. “

In this clinical study, the research team disrupted this immunosuppressive pathway with a drug called Plerixafor. The drug was administered iv continuously for one week to 24 patients with pancreatic cancer or colon cancer with a low tumor mutation load. All patients had advanced disease and biopsies of metastatic tumors were obtained before and after treatment.

When the team analyzed these patient samples, it found that critical immune cells had infiltrated the tumors during the time the patients were receiving plerixafor, including a cell type known to conjure up and organize key players in the fight against cancer. The finding was encouraging as the team noted changes that were also seen in patients whose cancer responded well to checkpoint inhibitors.

Jodrell, who led the planning and patient recruitment for the clinical trial, 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 these difficult-to-treat patients who treat cancer . “A clinical trial based on this study is nearing commencement of recruitment and will test the effects of combining Plerixafor with an approved checkpoint inhibitor.

Markers can predict the patient’s response to cancer immunotherapy

More information:
Biasci, D., et al., “CXCR4 Inhibition in Human Pancreatic and Colon Cancers Induces an Integrated Immune Response,” PNAS, Oct. 30, 2020. DOI: 10.1073 / pnas.2013644117 Provided by Cold Spring Harbor Laboratory

Quote: Giving the immune system a double boost against cancer (2020, October 30), accessed October 31, 2020 from

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