RE:RE:CD8+ TiLs and T-cell exhaustionMay 22, 2024 - New research has discovered an important breakthrough that may further attribute to 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.
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.
"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,"
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," Parish said.
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In this context pf PD-L1 negative tumors ONCY has shown with results from ONCY's AWARE-1 study that pelareorep treatment upregulated tumor PD-L1 expression, induced the generation and expansion of T cell clones, promoted tumor infiltration of CD8+ TiL cells, and increased the CelTIL score, a measure of tumor cellularity and inflammation associated with favorable clinical outcomes, thus overcoming any issue of 'tolerance' that may be experienced.
In so doing pelareorep is able to overcome an immunosuppressive TME, pelareorp is a critical 'facilitator' in 'priming' the adaptive immune system in advance of PD-1 blockade, thus turning a 'cold' tumor into a 'hot' tumor that is more much conducive for PD-1 blockade, and a more effective I/O therapy than either agent alone.