Eleonora Ghisoni
Image source: Ludwig Cancer Center
So how do these tumors evade immune clearance? Experiments revealed that the cancer cells of inflamed tumors respond to a standard combination of chemotherapy and olaparib—a drug utilized to treat BRCA-deficient ovarian cancer—by activating a molecular signaling pathway driven by an enzyme known as COX. The pathway induces the secretion of PGE2, a lipid that functionally disables and induces the suicide of TILs.
Treating mice bearing inflamed, DNA repair-deficient tumors with an existing COX-inhibitor along with olaparib and chemotherapy significantly extfinished survival. That survival time doubled when this combination was supplemented with checkpoint blockade immunotherapy, which activates anti-tumor TILs.
“Our findings have immediate and testable implications for the treatment of ovarian cancer,” declared Ghisoni. “They suggest that patients with inflamed, DNA repair-deficient tumors may be ideal candidates for immunotherapy trials, while those with suppressive tumors may benefit from new therapeutic strategies, like TREM2 inhibition.”
More generally, the findings underscore the importance of tarreceiveing both cancer cells and the immune cells that enable immune evasion.
Source: Ludwig Cancer Center
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