Credit: Immunity (2024). DOI: 10.1016/j.immuni.2024.04.026
New research has discovered an important breakthrough that may overcome cancer treatment resistance. The immune system has a naturally occurring ‘brake’ that tells the body to silence key killer immune cells called CD8+ T-cells as a safeguard to restrain excessive immune responses. Cancer cells are known to exploit this process, called exhaustion, by hijacking the immune system at this ‘off-switch’ to dampen down the immune attack on cancer, enabling cancer growth.
This latest research, published in Immunity and led by Peter Mac’s Group Leader Dr. Ian Parish, has discovered a second brake on the immune system called tolerance where cancer cells effectively prevent the immune system from getting started in the first place.
Dr. Parish said this breakthrough helps to understand why cancer treatments fail and opens the door to developing new treatments in the future.
“Current cancer immunotherapy treatments target the exhaustion phase of the immune response to revive pre-existing anti-cancer immunity. Unfortunately, the immune system fails to move into action in most cancers, meaning that these therapies won’t work because there is no anti-cancer immune response to revive,” he said.
“Our research suggests that a second, earlier ‘off-switch’ called tolerance may explain how many cancers resist current immunotherapies by blocking anti-cancer immunity from getting off the ground.
“We’re excited as these findings can be exploited for new treatments. Our next step is to understand if we can disrupt tolerance and engage the immune system to restart and attack those cancers resistant to treatment.”
This research was co-led with Professor Fabio Luciano, University of NSW and Professor Chris Goodnow, Garvan Institute of Medical Research. Professor Chris Goodnow, Head of the Immunogenomics Laboratory at Garvan, said this study has widespread implications.
“Exhaustion is known to be exploited by tumors, but we showed that tolerance is a separate brake also used by tumors to block anti-cancer immune responses at a much earlier point in the immune response,” he said.
“An exciting implication of our work is that tolerance may be hijacked by some tumors to completely block an immune response against the cancer, leading to a tumor without any T-cells in it.
“These types of tumors are the ones that resist current immunotherapies in the clinic. Targeting tolerance with a drug in the future could benefit people who don’t respond to current therapies.”
More information:
Willem Van Der Byl et al, The CD8+ T cell tolerance checkpoint triggers a distinct differentiation state defined by protein translation defects, Immunity (2024). DOI: 10.1016/j.immuni.2024.04.026
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New study shows how cancer cells exploit the immune system (2024, May 22)
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