Frontiers in Pharmacology (Feb 2023)
Palbociclib impairs the proliferative capacity of activated T cells while retaining their cytotoxic efficacy
- Claudia Arndt,
- Claudia Arndt,
- Antje Tunger,
- Antje Tunger,
- Rebekka Wehner,
- Rebekka Wehner,
- Rebekka Wehner,
- Rebecca Rothe,
- Rebecca Rothe,
- Eleni Kourtellari,
- Stephanie Luttosch,
- Katharina Hannemann,
- Stefanie Koristka,
- Liliana R. Loureiro,
- Anja Feldmann,
- Torsten Tonn,
- Torsten Tonn,
- Torsten Tonn,
- Theresa Link,
- Theresa Link,
- Theresa Link,
- Jan Dominik Kuhlmann,
- Jan Dominik Kuhlmann,
- Jan Dominik Kuhlmann,
- Pauline Wimberger,
- Pauline Wimberger,
- Pauline Wimberger,
- Michael Philipp Bachmann,
- Michael Philipp Bachmann,
- Michael Philipp Bachmann,
- Michael Philipp Bachmann,
- Marc Schmitz,
- Marc Schmitz,
- Marc Schmitz
Affiliations
- Claudia Arndt
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
- Claudia Arndt
- Mildred Scheel Early Career Center, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Antje Tunger
- National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Antje Tunger
- Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Rebekka Wehner
- National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Rebekka Wehner
- Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Rebekka Wehner
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Rebecca Rothe
- National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Rebecca Rothe
- Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Eleni Kourtellari
- Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Stephanie Luttosch
- Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Katharina Hannemann
- Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Stefanie Koristka
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
- Liliana R. Loureiro
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
- Anja Feldmann
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
- Torsten Tonn
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Torsten Tonn
- German Red Cross Blood Donation Service North-East, Institute for Transfusion Medicine, Dresden, Germany
- Torsten Tonn
- Experimental Transfusion Medicine, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Theresa Link
- National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Theresa Link
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Theresa Link
- Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Jan Dominik Kuhlmann
- National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Jan Dominik Kuhlmann
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Jan Dominik Kuhlmann
- Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Pauline Wimberger
- National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Pauline Wimberger
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Pauline Wimberger
- Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Michael Philipp Bachmann
- Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
- Michael Philipp Bachmann
- National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Michael Philipp Bachmann
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Michael Philipp Bachmann
- Tumor Immunology, University Cancer Center (UCC), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Marc Schmitz
- National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
- Marc Schmitz
- Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Marc Schmitz
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany
- DOI
- https://doi.org/10.3389/fphar.2023.970457
- Journal volume & issue
-
Vol. 14
Abstract
The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib is an emerging cancer therapeutic that just recently gained Food and Drug Administration approval for treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor (Her)2-negative breast cancer in combination with the ER degrader fulvestrant. However, CDK4/6 inhibitors are not cancer-specific and may affect also other proliferating cells. Given the importance of T cells in antitumor defense, we studied the influence of palbociclib/fulvestrant on human CD3+ T cells and novel emerging T cell-based cancer immunotherapies. Palbociclib considerably inhibited the proliferation of activated T cells by mediating G0/G1 cell cycle arrest. However, after stopping the drug supply this suppression was fully reversible. In light of combination approaches, we further investigated the effect of palbociclib/fulvestrant on T cell-based immunotherapies by using a CD3-PSCA bispecific antibody or universal chimeric antigen receptor (UniCAR) T cells. Thereby, we observed that palbociclib clearly impaired T cell expansion. This effect resulted in a lower total concentration of interferon-γ and tumor necrosis factor, while palbociclib did not inhibit the average cytokine release per cell. In addition, the cytotoxic potential of the redirected T cells was unaffected by palbociclib and fulvestrant. Overall, these novel findings may have implications for the design of treatment modalities combining CDK4/6 inhibition and T cell-based cancer immunotherapeutic strategies.
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