CXCR3 on transferred T cells enables vaccine-boosted adoptive T-cell therapy in solid tumors
Year: 2026
Type: preprint
Abstract: Adoptive T-cell therapy (ACT) has demonstrated marked clinical benefit in hematological malignancies but has limited efficacy against solid tumors. Cancer vaccines can improve ACT, but the mechanisms underlying this combination are poorly understood. Here, we combined ACT with chimpanzee adenovirus ChAdOx1 (ChAd) and modified vaccinia Ankara (MVA) encoding tumor antigens. Whereas PD1 blockade failed to improve ACT, the combination with ChAd/MVA vaccination drove durable regression of established tumors, correlating with expansion of tumor-reactive T cells in lymphoid organs and increased tumor infiltration by T cells. Mechanistically, ChAd priming induced CXCR3 ligands (CXCL10 and CXCL9) in the vaccine-draining lymph node, thereby recruiting transferred T cells to this node independently of cognate antigen. CXCR3 expression on the transferred T cells, but not on host cells, was required for the anti-tumor effect of the combination therapy and favored T-cell accumulation in the vaccine-draining lymph node and the tumor. These findings identify CXCR3 on the transferred T cells as a determinant of ACT plus vaccination synergy and provide a rationale for combining viral-vector vaccines with TCR-T therapies, and for selecting or engineering T cells to retain CXCR3 expression. One Sentence Summary Viral vector vaccines synergize with TCR-T cell therapy to control solid tumors in a CXCR3-dependent manner.
Authors: Vinnycius Pereira Almeida, Lucy C. Garner, Sara Abdel Malak, Amanda Wicki, James McAuliffe, Laurine Noblecourt, Silvia Panetti, Emily E. Steffke, Aneesha Bhandari, Lyn Yong, Ali Amini, Claire Hutchings, Francesco Andreata, Yuanqin Yang, Audrey Gérard, Matteo Iannacone, Ricardo A. Fernandes, Paul Klenerman, Benoit Van den Eynde, Carol Sze Ki Leung
Institutions: University of Oxford, Ludwig Cancer Research, Medawar Building for Pathogen Research, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Kennedy Institute of Rheumatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Ludwig Cancer Research, de Duve Institute, Walloon Excellence in Lifesciences and Biotechnology, UCLouvain
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1275925132, G2156607337, Developing an infection-blocking pan-coronavirus vaccine, G3522017107, Lokale Untersuchung der Lage und Orientierung von Organischen Molekülen an Festen und Flüssigen Oberflächen., G564868737, Geological pattern recognition and geodynamical analysis using 3D seismic data, Neural network statistical estimation for very broad coverage parsing, Distributed, Scalable, and Sustainable Digital Trust, G6124110148, G7289447374, (ICF)- IMMPROVE: Immune Memory and Mechanisms of Protection from Vaccines
OpenAlex ID: W7221474462