Authors
Laurine Noblecourt, Amanda Wicki, Ashwin Jainarayanan, Vinnycius Pereira-Almeida, James McAuliffe, Emily Steffke, Silvia Panetti, Hannah Fuchs, Ramiro A Ramirez-Valdez, Vineethkrishna Chandrasekar, Yanshu Cai, Sanne Boekestijn, Adrian V S Hill, Audrey Gerard, Marij J P Welters, Sjoerd H Van der Burg, Isabela Pedroza-Pacheco, Benoit J Van den Eynde, Carol Sze Ki Leung
Published in
Cancer cell. Oct 02, 2026. Epub Oct 02, 2026.
Abstract
Therapeutic cancer vaccines are increasingly tested in clinical settings alongside standard-of-care treatments that often include chemotherapy, yet whether chemotherapy synergizes with cancer vaccines remains unclear. Here, we tested heterologous prime-boost viral vector vaccines in combination with various chemotherapy regimens. Both carboplatin plus paclitaxel (CarboTaxol) and cyclophosphamide improve vaccine efficacy and enhance antigen-specific CD8+ T cell responses. These chemotherapies act as immunological adjuvants independently of tumor presence. Mechanistically, CarboTaxol induces an early, antigen-independent expansion of stem-like T cell factor 1 (TCF1)+CD8+ T cells, an effect also observed in patients with different cancer types. Genetic or pharmacological disruption of TCF1 impairs the immunological adjuvant effect of CarboTaxol. Adding programmed cell death 1 (PD-1) blockade to viral vector vaccines and CarboTaxol further improves tumor control and survival. Together, these findings identify a TCF1-dependent mechanism underlying the immune adjuvant effect of chemotherapy and provide a rationale for clinical evaluation of this triple combination therapy.
PMID:
42826713
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.
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