Details

Autor(en) / Beteiligte

• Heller, Simon
• Glaeske, Sarah
• Gluske, Katja
• Paul, Juliane
• Böhme, Annika
• Janzer, Andreas
• Roider, Helge Gottfried
• Montebaur, Anna
• Nicke, Barbara
• Lesche, Ralf
• von Ahsen, Oliver
• Politz, Oliver
• Liu, Ningshu
• Gorjánácz, Mátyás

Titel

Pan-PI3K inhibition with copanlisib overcomes Treg- and M2-TAM-mediated immune suppression and promotes anti-tumor immune responses

Ist Teil von

• Clinical and experimental medicine, 2023-12, Vol.23 (8), p.5445-5461

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The PI3K pathway is one of the most frequently altered signaling pathways in human cancer. In addition to its function in cancer cells, PI3K plays a complex role in modulating anti-tumor immune responses upon immune checkpoint inhibition (ICI). Here, we evaluated the effects of the pan-Class I PI3K inhibitor copanlisib on different immune cell types in vitro and on tumor growth and immune cell infiltration in syngeneic murine cancer models. Intermittent treatment with copanlisib resulted in a strong in vivo anti-tumor efficacy, increased tumor infiltration of activated T cells and macrophages, and increased CD8 +  T cell/regulatory T cell and M 1/ M 2 macrophage ratios. The strong in vivo efficacy was at least partially due to immunomodulatory activity of copanlisib, as in vitro these murine cancer cells were resistant to PI3K inhibition. Furthermore, the combination of copanlisib with the ICI antibody anti-PD-1 demonstrated enhanced anti-tumor efficacy in both ICI-sensitive and insensitive syngeneic mouse tumor models. Importantly, in an ICI-sensitive model, combination therapy resulted in complete remission and prevention of tumor recurrence. Thus, the combination of ICIs with PI3K inhibition by intermittently dosed copanlisib represents a promising new strategy to increase sensitivity to ICI therapies and to treat human solid cancers.