ArticleJournal for immunotherapy of cancer2025
4-1BB agonist targeted to fibroblast activation protein α synergizes with radiotherapy to treat murine breast tumor models.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Review
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- Radiation-Induced Alterations in Cancer-Associated Fibroblasts: Drivers of Tumor Radioresistance and Therapeutic Targets.Biomolecules · 2026Review
- Cancer-associated fibroblast targeting therapies as a tool to enhance responses to radiotherapy and immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Preclinical evaluation of FAP-targeted PET imaging to investigate CAF responses to radiotherapy.Cancer imaging : the official publication of the International Cancer Imaging Society · 2026Article
- Article
- Phenotypic and ultrastructural heterogeneity of fibroblasts and vasculogenic mimicry in rectal adenocarcinoma following neoadjuvant chemoradiotherapy.Histochemistry and cell biology · 2025Article
- Cancer-associated fibroblast secreted DKK1 promotes the immunosuppressive tumor microenvironment and colorectal cancer resistance to chemotherapy.Cancer letters · 2025Article
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Abstract
backgroundIonizing radiation (IR) is a double-edged sword for immunotherapy as it may have both immunosuppressive and immunostimulatory effects. The biological effects of IR on the tumor microenvironment (TME) are a key factor for this balance. Fibroblast activation protein (FAP) is expressed on the surface of cancer-associated fibroblasts (CAF) in many cancer types and its abundance is associated with the poor immune response to immune-checkpoint-blockade in patients. We hypothesized that IR increases FAP expression in CAFs, therefore the combination of IR with targeted immunomodulators such as an agonistic anti-FAP-4-1BBL fusion protein could enhance the immune-mediated antitumoral effects of these treatments.
methodsThe murine transplantable TS/A tumor-cell-line co-engrafted with CAFs was used to investigate increases in FAP expression in tumors following irradiation using immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and multiplex tissue immunofluorescence. One lesion of bilateral tumor-bearing mice was only locally irradiated or combined with weekly injections of the bispecific muFAP-4-1BBL fusion protein (a mouse surrogate for RG7826). Tumor sizes were followed over time and TME was assessed by flow cytometry. Selective monoclonal antibody (mAb)-mediated depletions of immune cell populations, neutralizing interferon alpha/beta receptor 1 (IFNAR-I) IFNAR and interferon (IFN)-γ mAbs and gene-modified mice (4-1BB
resultsIrradiation of TS/A+CAF tumors in mice showed an increase in FAP levels after local irradiation. A suboptimal radiotherapy regimen in combination with muFAP-4-1BBL attained primary tumor control and measurable abscopal effects. Immune TME landscape analyses showed post-treatment increased infiltration of activated immune cells associated with the combined radioimmunotherapy treatment. Efficacy depended on CD8
conclusionIncreased FAP expression in the TME as a result of radiotherapy can be exploited to target agonist 4-1BB immunotherapy to malignant tumor lesions using an FAP-4-1BBL antibody fusion protein.
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