Cancer immunotherapy could be improved by using vaccines alongside checkpoint inhibitors to activate two types of T cells, according to a new US study.
Dr Robert D. Schreiber, of Washington University School of Medicine, St Louis, said immunotherapy had huge potential for cancer treatment, but the major stumbling block is to make it more widely effective.
The study, published in Nature, demonstrates for the first time that helper T cells are essential in cancer immunotherapy because they recognise cancer as a threat and recruit killer T cells to mount an attack. Without the helper T cells, the immune system typically does not fully respond to fight cancer.
“Activating killer T cells alone is not enough,” said Dr Schreiber. “To work better for all patients, we think effective cancer vaccines and immunotherapy drugs must activate both the killer and helper T cells.”
Existing cancer vaccines and immune checkpoint therapies are designed with a solid understanding of MHC class I molecules, which activate killer T cells.
However, this new study examines MHC class II molecules, which activate the helper T cells. It also reveals how to harness knowledge of both of these components of the immune system, ensuring that the helper and killer T cells can work together to eliminate the cancer and spare healthy tissues.
During the study, the research team developed a computer program that can predict, for the first time, which mutant proteins on a patient’s tumour will specifically activate helper T cells. This is an important development for harnessing helper T cells in cancer immunotherapy, they add.
When they studied mice with models of human cancer, the researchers were able to show that immune checkpoint therapy is more effective when helper T cells are activated along with killer T cells. They went on to establish that the most effective anti-tumour responses occurred when immune checkpoint therapy was combined with a vaccine, incorporating targets for both helper and killer T cells that are specific to antigens in the patient's tumour.
Alspach, E., Lussier, D.M., Miceli, A.P., Kizhvatov, I., DuPage, M., Luoma, A.M., Meng, W., Lichti, C.F., Esaulova, E., Vomund, A.N., Runci, D., Ward, J.P., Gubin, M.M., Medrano, R.F.V., Arthur, C.D, White, J.M., Sheehan, K.C.F., Chen, A., Wucherpfennig, K.W., Jacks, T., Unanue, E.R., Artyomov, M.N., Schreiber, R.D. (2019) “MHC-II neoantigens shape tumor immunity and response to immunotherapy”, Nature, doi: 10.1038/s41586-019-1671-8
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