Cell: Is oncology immunotherapy working? Look at this "signal light."

In the body's immune system, T lymphocytes are able to attack cancer cellsBut T cells have inhibitory receptors that, like brakes, inhibit the activity of T cellsAntibodies that target CTLA-4 or PD-1, known as immunocheckpoint inhibitors, can lift the brakes on immune cells and have become a first-line treatment for some cancersunfortunately, even in the best treatment cases, such as melanoma, less than 30% of patients respond to immunoosine inhibitors, and some patients relapse or worsen after a period of treatmentWhy is the brake lifted and cannot pass without obstruction? How to get more patients to benefit from immunotherapy is a challenge for many scientistsProfessor Andy Minn of the Abramson Cancer Center at the University of Pennsylvania, who led the study, and colleagues have previously found that interferon (IFN) signals play an important role in tumor resistance to immunocheckpoint inhibitorsinterferons are named for their ability to interfere with the spread of the virusNormally, interferon activates the immune system when a virus attacks the bodyHowever, interferons are a "two-faced" one, for example, in the case of chronic viral infections, which can also inhibit the immune systeminterferon also behaves quite "contradictory" in the immune response to anti-tumorInterferon enhances the identification of immune cells to cancer cells, while persistent interferon signals cause T-cell depletion and immunosuppressionin the past, the team found that when interferon suppresses the immune system, cancer cells block and manipulate the signalSingle-cell sequencing and other results showed that in drug-resistant tumor cells, interferon-stimulating genes (ISG) were expressed with increased resistance characteristics, while interferon-related gene expression decreased in immune cellstumor cells are resistant to immunotherapy through interferon signals (Picture: References1))based on the strong and weak balance of this signal, may improve the effectiveness of immunotherapy if it increases the "green light" signal of interferon in the immune system, or weakens the "red light" signal in tumor cells?researchers tested the latter treatment in a variety of mouse tumor models, including melanoma, breast cancer and colorectal cancerThey blocked the interferon signaling pathway in tumor cells by gene knockout, and when immunotherapy such as PD-1 inhibitors or CAR-T cells was used, the tumor-killing effect of immune cells improved significantly, thus prolonging the survival of mice blocking interferon signals of tumor cells in colon cancer model mice, improving the effectiveness of anti-PD-1 therapy (Photo source: References) further explore the mechanism of regulating interferon signals, and the researchers found that after blocking the interferon pathways of tumor cells, the exhaustion T cells function increased, producing stronger interferon signals, and promoting the maturation of natural killer cells In other words, when the interferon signal of cancer cells is turned off, both adaptive and inherent immune responses are "released" blocking the interferon signals of tumor cells, adaptive immunity and inherent immunity were enhanced (Photo: References) analyzed genome sequencing data in cancer patients, and the researchers found that in non-small cell lung cancer patients who received a combination of PD-1 inhibitors and CTLA-4 inhibitorthes, the response to immunotherapy was cortifyed with the patient's interferon signaling pathway gene variant In other words, interferon signals may be used as biomarkers to predict whether patients will benefit from immunotherapy team hopes to find safer and more effective signal regulation, especially to suppress tumor cell signaling A phase 2 clinical trial has been conducted in PD-1-positive lung cancer patients, according to the University of Pennsylvania We look forward to more cancer patients eventually benefiting from effective treatments in the near future References: Joseph Benci et al., (2019) Opposing Functions of The Interferon and The Innate Immune Responses to Cancer Immune Checkpoint Cell DOI: 10.1016/j.cell.2019.07.019 .2 Balance of "Stop" and "Go" Signaling Be Key to Cancer Immunothe Response Retrieved Aug 13, 2019, from Joseph Benci et al., (2016) Tumor Interferon Interfering Signal Sa Multigenic Resistance To ImmunE Checkpoint Blockade Cell DOI: 10.1016/j.cell.2016.11.022