An international team of researchers has revealed a new mechanism to ‘activate’ the immune system against cancer. The mechanism allows immune cells to detect and destroy cancer cells better than before, according to a study led by Prof. Nick Haining, of Harvard Medical School, and co-authored by Prof. Erez Levanon, doctoral student Ilana Buchumansky, of the Mina and Everard Goodman Faculty of Life Sciences at Bar-Ilan University.
The study involves a mechanism which recurrently serves the cell by marking human virus-like genes in order to avoid identifying them as viruses. Now, Prof. Levanon, together with the Harvard team, has discovered that when inhibiting this mechanism, the immune system can be harnessed to fight cancer cells in a particularly efficient manner, and most effectively in lung cancer and melanoma.
“We found that if the mechanism is blocked, the immune system is much more sensitive. When the mechanism is deactivated, the immune system becomes much more aggressive against the tumor cells,”
Immune Checkpoint Blockade
In recent years, a new generation of cancer drugs has been developed which blocks proteins that inhibit immune activity against malignant tumors. Referred to as immune checkpoint therapy, these drugs have shown exceptional success in several tumor types.
The 2018 Nobel Prize in Medicine was awarded to immunologists James Allison and Tasuku Honjo, who discovered the key genes of this mechanism. Despite this achievement, the current generation of drugs helps only a small number of patients, while most of the drugs fail to cause the immune system to attack the tumor.
It is believed that the new discovery may allow enhanced activity of the immune system to attack cancer cells. A number of companies have already begun research to screen for drugs that will operate on the basis of this discovery.
Jeffrey J. Ishizuka, Robert T. Manguso, Collins K. Cheruiyot, Kevin Bi, Arpit Panda, Arvin Iracheta-Vellve, Brian C. Miller, Peter P. Du, Kathleen B. Yates, Juan Dubrot, Ilana Buchumenski, Dawn E. Comstock, Flavian D. Brown, Austin Ayer, Ian C. Kohnle, Hans W. Pope, Margaret D. Zimmer, Debattama R. Sen, Sarah K. Lane-Reticker, Emily J. Robitschek, Gabriel K. Griffin, Natalie B. Collins, Adrienne H. Long, John G. Doench, David Kozono, Erez Y. Levanon & W. Nicholas Haining
Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade
Nature volume 565, pages 43–48 (2019)
Image: Wellcome Images