Cancer Cell: Reveals the molecular mechanisms by which interferon gamma directs melanoma patients to respond to cancer immunotherapy.

September 14, 2020 // -- In a recent study published in the international journal Cansr Cell, scientists from the University of California and other institutions revealed the molecular mechanisms by which interferon gamma (IFN-gamma) guides the therapeutic response of patients with malignant melanoma, all of which are treated with immuno-checkpoint blockers, an immune-stimulus molecule that helps activate the immune cellular function of host bodies.
Photo Source: National Institutes of Health researchers point out that the two main drivers that help maintain immune system function may help effectively attack cancer, and that the level of T-cell immersion in tumors stems from the release of immune checkpoint blockers and the signaling of the corresponding downstream interferon gamma, blocking the signaling of immune checkpoints that were previously thought to limit the attack on cancer cells or drive interferon, thereby amplifying the body's anti-tumor immune response and thus inducing a clinical response induced by cancer immunotherapy.
researcher Antoni Ribas said: 'Our study found that when the pre-immune response against cancer is amplified, immuno-checkpoint blocking therapy works, and cancer cells can block the way the immune system attacks cancer cells through immune checkpoints (CTLA-4 and PD-1), and whenever an immune checkpoint is released, the increase in immune activation depends on the strength of T-cells producing immune-activated cytokines, which can cause more than 600 genes to be activated, which in turn causes the body's immune response to be activated.
Now, despite the huge success of scientists in cancer immunotherapy, which uses the host's immune system to better attack cancer cells, only a small percentage of patients benefit; researchers want to continue to investigate and use techniques such as genome sequencing to better understand the effects of immunosuppression on cancer patients so that they can overcome limitations and extend the treatment to more patients.
the study, researchers studied 101 melanoma patients who received anti-PD-1 antibody nalvutin, navu-monoantibodies, and anti-CTLA-4 antibodies, Iplimma combination therapy, who sequenced the genome of melanoma tissue in their bodies at DNA and RNA levels to analyze the living tissue characteristics of the baseline and treatment, navu monoantitor and Iprimma. Cancer immunotherapy drugs: Before and during the treatment of participants, the researchers looked at changes in the tumor tissue characteristics of their bodies to analyze the expression of genes in patients who showed clinical responses and did not show clinical responses, which may allow them to observe mechanisms that change over time in patients' immune responses, while also focusing on how cancer cells activate genes when the immune system is active, and then discover interferon genes, they noted. The ability to react to interferon gamma by turning on or off the expression of a series of genes is preserved in most cancer cells.
The researchers say they will continue to study the interferon gene in depth later in life as a new way to predict patients' responses to immunotherapy, and they want to find a new combination therapy to induce interferon signaling and apply it to more cancer patients.
original source: Catherine S. Grasso, Jennifer Tsoi, Mykola Onyshchenko, et al. Conserved Interferon-Signaling Drives Clinical Response to Immune Checkpoint Blockade Therapy in Melanoma, Cancer Cell (2020). DOI: 10.1016/j.ccell.2020.08.005.