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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Thursday, December 1, 2022
Interleukin 17 (IL-17) may play a significant role in the poor prognosis and outcome associated with treatment of patients with hormone receptor–positive, HER2-positive breast cancer, according to a preclinical study presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 1144). “Our findings prompt the initiation of clinical trials comparing standard-of-care CDK4/6 inhibition plus letrozole versus CDK4/6 inhibition plus letrozole and an [IL-17] blocker (at least three of which are currently approved for psoriasis treatment) in patients with hormone receptor–positive, HER2-negative breast cancer,” said Lorenzo Galluzzi, PhD, of Weill Cornell Medicine, New York, and colleagues.
The study authors used an immunocompetent mouse model whose biology recapitulates hormone receptor–positive, HER2-negative breast cancer in humans. This model included a cold tumor microenvironment with poor sensitivity to PD-1 blockers. Furthermore, the group used three different cohorts of patients with breast cancer from The Cancer Genome Atlas for in silico analysis.
The researchers reported that within their mouse model, circulating IL-17 seemed to be correlated with poor overall survival; however, blocking the γδ T-cell receptors or neutralizing IL-17 seemed to improve the effectiveness of CDK4/6 inhibitors. When the group analyzed data from The Cancer Genome Atlas, they found patients with IL-17 signaling had a poor overall survival and evidence of immunosuppression within the tumor microenvironment. The group also reported a correlation between γδ T-cell infiltration and tumor grade from biopsies of patients with hormone receptor–positive, HER2-negative breast cancer. Finally, the group also found that circulating chemokine ligand 2 levels may be augmented during CDK4/6 therapy in patients with progressive disease. Based on these data, the authors suggested that using IL-17 blockers may improve outcomes for patients with this type of breast cancer but called for clinical trials to confirm their preliminary results.
Disclosure: No disclosure information was provided.
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