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Published (Version of Record)CC BY V4.0, Open Access
Report
CD4+T cells drive an inflammatory, TNF-a/IFN-rich tumor microenvironment responsive to chemotherapy
Cell Reports, Vol.41(13), 111874
Elsevier
2022
PMID: 36577370
Abstract
While chemotherapy remains the first-line treatment for many cancers, it is still unclear what distinguishes responders from non-responders. Here, we characterize the chemotherapy-responsive tumor microenvironment in mice, using RNA sequencing on tumors before and after cyclophosphamide, and compare the gene expression profiles of responders with progressors. Responsive tumors have an inflammatory and highly immune infiltrated pre-treatment tumor microenvironment characterized by the enrichment of pathways associated with CD4+ T cells, interferons (IFNs), and tumor necrosis factor alpha (TNF-a). The same gene expression profile is associated with response to cyclophosphamide-based chemotherapy in patients with breast cancer. Finally, we demonstrate that tumors can be sensitized to cyclophosphamide and 5-FU chemotherapy by pre-treatment with recombinant TNF-a, IFNg, and poly(I:C). Thus, a CD4+ T cell-inflamed pretreatment tumor microenvironment is necessary for response to chemotherapy, and this state can be therapeutically attained by targeted immunotherapy.
Details
- Title
- CD4+T cells drive an inflammatory, TNF-a/IFN-rich tumor microenvironment responsive to chemotherapy
- Authors/Creators
- Caitlin M. Tilsed - Institute for Respiratory HealthNicola Principe - Institute for Respiratory HealthJoel Kidman - Institute for Respiratory HealthWee Loong Chin - Sir Charles Gairdner HospitalM. Lizeth Orozco Morales - Natl Ctr Asbestos Related Dis, Nedlands, WA 6009, AustraliaRachael M. Zemek - The Kids Research Institute AustraliaJonathan Chee - Institute for Respiratory HealthRasa Islam - Asbestos Diseases Research InstituteVanessa S. Fear - The Kids Research Institute AustraliaCatherine Forbes - The Kids Research Institute AustraliaWayne J. Aston - Asbestos Diseases Research InstituteMaud Jansen - Natl Ctr Asbestos Related Dis, Nedlands, WA 6009, AustraliaAbha Chopra - Murdoch UniversityTimo Lassmann - The Kids Research Institute AustraliaAnna K. Nowak - Natl Ctr Asbestos Related Dis, Nedlands, WA 6009, AustraliaScott A. Fisher - Institute for Respiratory HealthRichard A. Lake - Institute for Respiratory HealthW. Joost Lesterhuis - The Kids Research Institute Australia
- Publication Details
- Cell Reports, Vol.41(13), 111874
- Publisher
- Elsevier
- Grant note
- Raine Research Foundation iCare Dust Diseases Board Cancer Council WA; Cancer Council Western Australia Simon Lee Foundation WA Department of Health NHMRC; National Health and Medical Research Council (NHMRC) of Australia UWA
- Identifiers
- 991005592876607891
- Copyright
- © 2022 The Author(s)
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Report
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- Molecular Biology & Genetics