Studies highlight ‘potential new targets for immunotherapy’
Three separate studies have revealed potential new avenues for research into immunotherapy.
Two have highlighted molecules that may help cancer cells evade the immune system. While the other suggests that the effects of an experimental breast cancer drug could be boosted by immunotherapy.
All 3 studies were published in the journal Nature.
Immunotherapy drugs harness the power of the immune system to attack cancers. The most common type release the immune system’s inbuilt ‘brakes’, freeing immune cells to attack the tumour.
In two separate studies researchers looked at one set of ‘brakes’ – controlled by a checkpoint molecule called PD-L1 – which can prevent the immune system from launching an effective attack against cancer cells.
They found that PD-L1 relies on two molecules called CMTM4 and CMTM6 to carry out its job in lab-grown cancer cells. These molecules made PD-L1 more stable, enhancing the ability of tumour cells to escape attack by certain immune cells.
Professor Ton Schumacher, who led the work at the Netherlands Cancer Institute, said that blocking these molecules could boost the immune response in a similar way to existing drugs that target PD-L1. “Blocking both molecules could even be superior,” he added, although he cautioned that it’s too early to say whether this will eventually be developed into a treatment.
Dr Marian Burr, a Cancer Research UK-funded scientist based at the Peter MacCallum Cancer Centre in Australia and lead author of the second Nature study, said she was pleased to see Schumacher's co-discovery using different methods as this provided validation of the findings.
"We have identified that binding of a protein called CMTM6 to PD-L1 is critical to enable cancer cells to maintain PD-L1 at their surface, thus shielding the cancer from the immune system," she said.
"These findings provide new insight into the way in which the PD-L1 immune checkpoint is regulated and opens up a new avenue for the development of immunotherapy agents that restrict PD-L1 expression by targeting CMTM6."
Dr Edd James, a Cancer Research UK-funded expert on immunotherapy from the University of Southampton, said: “The findings from this research raise an exciting prospect as they indicate possible new targets for immunotherapy, which may work alone or in combination with current checkpoint therapies.
“How well this would work isn’t yet known and it will be important to conduct further experiments to work out how effective disrupting the interaction between CMTM6 and 4 and PD-L1 might be.”
The third study, from the Dana-Farber Cancer Institute and Brigham and Women's Hospital in the US, looked at a targeted cancer drug that stops tumour cells from growing.
This drug was expected to stop tumours from getting any bigger, but lead researcher Dr Shom Goel said that some patients’ breast cancers also shrank following treatment in early stage clinical trials.
To examine what could be behind this effect, the researchers looked at mice with several types of cancer and treated them with the experimental breast cancer drug, called abemaciclib.
The drug caused tumours to shrink, halting cell growth as expected but also causing the immune system to attack the cancer. And when the drug was combined with a checkpoint immunotherapy the tumours in mice shrank even more.
Dr James described these findings as “very interesting” as they indicate a potential way to alert the tumour to the immune system, enabling stronger anti-tumour responses.
This dual action, he said, has the potential to both prevent tumour growth while also increasing the immune response to the cancer cells.
He added that further studies are needed to better understand how this could enhance checkpoint inhibitor immunotherapy.
This article was updated on 23.08.2017 to include the work by Burr et al.
Mezzadra, R. et al. (2017). Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature. DOI: 10.1038/nature23669
Goel, S. et al. (2017). CDK4/6 inhibition triggers anti-tumour immunity. Nature. DOI: 10.1038/nature23465
Burr, M. L. et al. (2017). CTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity. Nature. DOI: 10.1038/nature23643