Cell: manipulation of interferon signal is expected to make cancer immunotherapy effective

August 14, 2019 / Biovalley BIOON / - -- in a new study, researchers from the University of Pennsylvania found that a key signaling pathway that tells the immune system to fight cancer can also be used by cancer cells to suppress the immune system They said this increased understanding could serve as a biomarker to help predict which patients might respond to immunotherapy They also showed how changing this balance could have a potential impact on the treatment itself, because blocking this signal in cancer cells helps immune cells fight tumors in a variety of preclinical cancer models The relevant research results were published in the cell Journal on August 8, 2019 The paper title is "operating functions of interaction coordinate adaptive and internal immune responses to cancer immune checkpoint blockade" Picture from cell, 2019, DOI: 10.1016/j.cell.2019.07.019 This study focuses on interferon (IFN) signaling pathway Interferon usually helps activate the immune system to protect cells from viruses, so it's named because they actually interfere with the ability of the virus to spread However, interferon can also inhibit the immune system Dr Andy J Minn, associate professor of radiation oncology and director of the center for immunotherapy, immune signaling and radiology at the University of Pennsylvania, the paper's co-author, said, "this contradictory effect has emerged in other diseases such as chronic viral infection, but our study shows how cancer cells can use the inhibitory properties of interferon to interfere with cancer immunotherapy." The new study builds on a study published by Minn and his team in the journal Cell in 2016 (cell, 2016, DOI: 10.1016 / J.Cell 2016.11.022), in which they initially identified the role of interferon in cancer immunotherapy resistance In this new study, the researchers found that when interferon suppresses the immune system, cancer cells intercept and manipulate the signal However, when interferon is allowed to send signals to the immune system, immune cells are able to do their job and kill tumors Understanding the balance between interferon signaling and cancer cells may provide a biomarker for the effectiveness of immunotherapy "If we know that this signal is biased toward immune cells or cancer, then we may be able to better predict whether patients are likely to respond," Minn said In the case of cancer cells with stronger interferon signal, there may be a treatment Blocking this signal in a tumor only leaves a "go" signal, which activates the immune system to attack the cancer This is the case when scientists tested this view in preclinical models of melanoma, breast cancer, and colorectal cancer treated with PD-1 inhibitors or car-t cells "Interferon signaling is present in most human cancers, so it may have a broader application," Minn said The next step is to find new and safe ways to make interferon's "release" signal stronger, or block interferon's "stop" signal A clinical trial test showed that a second protocol for lung cancer patients, blocking interferon stop signals, had recruited patients in Pennsylvania (nct03425006) (BIOON Com) reference: 1 Joseph L Benci et al Operating functions of interaction coordinate adaptive and internal immune responses to cancer immune checkpoint blockade Cell, 2019, doi:10.1016/j.cell.2019.07.019 2.Balance of “Stop” and “Go” Signaling Could Be Key to Cancer Immunotherapy Response https://www.pennmedicine.org/news/news-releases/2019/august/balance-of-stop-and-go-signaling-could-be-key-to-cancer-immunotherapy-response