Mount Sinai team maps a key combo role for new checkpoint drugs

Jeremy Price

A new mouse study conducted by scientists at The Tisch Cancer Institute of the Icahn School of Medicine at Mount Sinai has pointed to another way that checkpoint inhibitors can play an important part of a combination therapy in attacking cancer.

Their focus is on Langerhans cells, which abide in the skin and can repair damage to DNA. Following radiation therapy, which damages the skin, these largely dormant, radiation-resistant Langerhans cells recruit regulatory T cells--Tregs--to the site of the damage, promoting resistance to the treatment by dampening an immune response.

The investigators, though, then "mimicked" the effective of checkpoint inhibitors which are designed to amp up an immune system attack, overcoming the resistance mechanism. Langerhans cells, they add, are resistant to radiation treatment because they contain a protective protein.

Checkpoint inhibitors are "synergized by the addition of radiation, which can expose the tumor so it can better be targeted by the immune system," says the study's lead author, immunologist Jeremy Price. "By combining these treatments, the ability of Langerhans cells to use the immune system to protect cancers will be overwhelmed."

While the Langerhans cells are specific to the skin, playing a role in melanoma, the researchers believe that the same approach should work equally well in other tumors, in which dendritic cells play a similar salvaging role in recruiting Tregs as the Langerhans cells.

"Any treatment that prevents tumor infiltrating regulatory T cells from being produced, such as immunotherapy, will improve the outcome from radiation treatment--and that will save lives," Dr. Price added.

Checkpoint inhibitors have been coming on strong over the past year. Merck ($MRK) and Bristol-Myers Squibb ($BMY) are both broadening approvals of their pioneering PD-1 checkpoint drugs while Roche and AstraZeneca ($AZN) have been following up on the PD-L1 side of the immuno-equation. Through it all, researchers have been pointing to a variety of new combination approaches that they believe will extend survival rates for patients.

- here's the release
- read the journal abstract

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