EMBO Rep: Discovering a new immune brake --- EGR4, promising new anti-cancer immunotherapy

April 5, 2020 /PRNewswire BIOON/--- Immune System is like a carefully tuned machine with its own built-in "brake" that prevents it from overreacting and causing excessive inflammation in otherwise healthy tissues However, this preventive safety net is very fragile, especially in cancer, where tumor cells constantly brake, allowing tumor cells to evade immune testing Scientists have discovered several molecules that naturally suppress immune activity, opening the door to immunotherapy, a potentially efficient way to attack cancer cells using the immune system In order for immunotherapy to fulfil its full potential in human patients, it is also important to learn more about the factors that contribute to anti-cancer immunity Now, in a new study, researchers at the Lewis-Katz School of Medicine at Tempe University and fox-Zeiss Cancer Center have for the first time found that a molecule called EGR4, which plays an important role in male fertility, acts as a key brake for immune activation They also found that removing EGR4, which effectively releases this critical brake, promotes the activation of killer T-cells, which soak and attack tumor , thereby boosting anti-cancer immunity The findings were recently published in the journal EMBO Report, entitled "Suppreion of Ca2 plus ignal by EGR4 control Th1 azol and anti-cancer immunity in vivo" images from EMBO Report, 2020, doi:10.15252/embr.201948904 "Other early growth-reactive proteins (EGR) are important for the activity of T-cells, but whether EGR4 is also immune-enabled is significantly ignored," explains co-author Professor Jonathan Soboloff of the Fels Institute for Cancer Research and Molecular Biology at The Lewis-Katz School of Medicine at Tempe University Our study reveals a new aspect of the importance of EGR4 "Dr Soboloff and his team worked with Dr Dietmar J K app
e and their research team at Fox Chase Cancer Center on the effects of EGR4 expression in immune cells In the initial experiment, the researchers found that T-cell activation was associated with EGR4 upwards They then found that knocking out or removing EGR4 from immune cells led to a sharp increase in calcium signals and the expansion of the Th1 cell population Th1 cells respond to the presence of foreign entities, including tumor cells, activating killer T-cells and then removing intruders "We know from previous studies that T-cells control calcium signals, and that calcium signals can drive T-cell activation when calcium levels rise in cells," Dr Soboloff said Soboloff and K
app
e labs then studied the functional importance of EGR4 in cancer immunity by using a relayed mouse model that the of melanoma, in which some host animals lack EGR4 expression Compared to mice with typical EGR4 levels, EGR4 knockout mice showed evidence of increased number of Th1 cells and increased anti-cancer immunity In particular, EGR4 knocks out mice with lower lung tumor burden and less cancer cell metastasis than mice with normal EGR4 expression In future research, the Soboloff team and the Kappe team plan to further explore the EGR4 targeting strategy Given the many functions of the EGR pathway, it is difficult to develop specific targetEGR4 reagents "However, removing EGR4 specifically from the patient's T cells and then putting them back into the patient's body may be a viable immunotherapy treatment," Dr K
app
e said (Bio Valley Bioon.com) References: 1.Jayati Mookerjee-Bau et al.
Suppreion of Ca2 plus ignal by EGR4 control Th11 and anti-cancer immunity in vivo EMBO Report, 2020, doi:10.15252/embr.201948904.
2 Blake on immune activity, raiing new poibilitie for anticancer therapy
http://medicalxpre.com/new/2020-03-immune-poibilitie-anticancer-therapy.html