Researchers studied the process in mouse and human breast tumors and identified 16 immune checkpoint genes that encode proteins designed to inactivate cancer-killing T-cells.
“We’re among the first to actually study the tumor that survives post-chemotherapy, which is called the residual disease, to see what kind of immunotherapy targets are expressed,” said the study’s first author Ashkan Shahbandi, an M.D./Ph.D. student in Jackson’s lab.
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The tumors that respond the worst to chemotherapy enter a state of dormancy – called cellular senescence – instead of dying after treatment. Researchers found two major populations of senescent tumor cells, each expressing different immune checkpoints activated by specific signaling pathways. They showed the expression of immune evasion programs in tumor cells required both chemotherapy to induce a senescent state and signals from non-tumor cells.
They tested a combination of drugs aimed at these different immune checkpoints. While response could be improved, these strategies failed to fully eradicate the majority of tumors.
“Our findings reveal the challenge of eliminating residual disease populated by senescent cells that activate complex immune inhibitory programs,” Jackson said. “Breast cancer patients will need rational, personalized strategies that target the specific checkpoints induced by the chemotherapy treatment.”
Source: Eurekalert
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