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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Wednesday, October 30, 2024
Wen-Chi Yang, MD, of the National Taiwan University Hospital, Taipei, and colleagues evaluated whether the integration of radiotherapy with CDK4/6 inhibitors can enhance the efficacy of immunotherapy in patients with triple-negative breast cancer by modulating the tumor microenvironment. The results of this trial suggest this treatment strategy may demonstrate synergistic potential in this patient population.
“Combined CDK4/6 inhibitors with radiotherapy enhance antitumor effects of anti–PD-L1 immunotherapy in triple-negative breast cancer through increasing secretion of interferon-gamma and modulation of tumor microenvironments via recruiting CD4- and CD8-positive T cells, as well as M1-type tumor-associated macrophage[s],” concluded the investigators, at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 164).
Human triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-453, and MDA-MB-468, as well as the mouse triple-negative breast cancer cell line 4T1, were used to evaluate how the CDK4/6 inhibitor abemaciclib may sensitize breast cancer to radiotherapy. Using the mouse model, the investigators evaluated the antitumor effects of anti–PD-L1 antibodies combined with radiotherapy and abemaciclib as well as the levels of tumor-infiltrating lymphocytes and interferon-gamma.
Whereas abemaciclib did not appear to alter PD-L1 expression in all cell lines, just one 8 Gy fraction of radiotherapy appeared to increase its expression on the surface of tumor cells. However, the combination of radiotherapy, anti–PD-L1 antibodies, and abemaciclib significantly decreased tumor growth (P < .05) and increased circulating interferon-gamma levels (P < .001) in treated mouse cells compared with control, radiotherapy alone, abemaciclib with anti–PD-L1 antibodies, abemaciclib with radiotherapy, and anti–PD-L1 antibodies with radiotherapy.
Furthermore, this triplet combination significantly increased the proportion of tumor-associated macrophages (P < .001), as well as CD4- (P < .05) and CD8-positive (P < .01) T cells when compared with the control group. Of note, an increase in monocyte chemoattractant protein-1 macrophages was identified among cell lines treated with the investigational combination compared with the other four treatment arms.
Disclosure: Dr. Yang reported no conflicts of interest.
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