Katharina Buczek
In turn, a problem akin to “whack-a-mole” is created for immunotherapy drugs– or checkpoint inhibitors– since they may eliminate tumor cells that express one checkpoint but miss other tumor cells that have various checkpoints.
“We found that they [breast cancers] avoid immune clearance by expressing a complex, redundant program of checkpoint genes and immune modulatory genes. The tumor completely changes after chemotherapy treatment into this thing that is essentially built to block the immune system,” explained James Jackson, a corresponding author of the study.
Then, following this discovery, the team studied this process in mouse models as well as human breast tumors. The researchers ultimately identified 16 immune checkpoint genes that are responsible for encoding proteins designed to disable T-cells– which help protect the body from infection and fight off cancer.
Additionally, the tumors that do not respond to chemotherapy– and survive rather than die after treatment– then enter a dormancy state known as cellular senescence. The team found two distinct major populations of these senescent tumor cells. Each of the populations expressed differing immune checkpoints, which are activated via specific signal pathways.
The researchers did also test a combination of drug therapies in hopes of targeting the various immune checkpoints. Unfortunately, though, the strategy was still unable to completely eradicate most of the tumors– underscoring how personalized these therapies need to become for patient care.
“Our findings reveal the challenge of eliminating residual disease populated by senescent cells that activate complex immune inhibitory programs,” Jackson concluded.
“Breast cancer patients will need rational, personalized strategies that target the specific checkpoints induced by the chemotherapy treatment.”
To read the study’s complete findings, which have since been published in Nature Cancer, visit the link here.
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