ArticleEBioMedicine2017
Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis.
Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- Mesothelin as a biomarker and potential therapeutic target in rheumatoid arthritis bone destruction.Cell reports. Medicine · 2025Article
- Public neoantigens in breast cancer immunotherapy (Review).International journal of molecular medicine · 2024Review
- Mesothelin promotes brain metastasis of non-small cell lung cancer by activating MET.Journal of experimental & clinical cancer research : CR · 2024Article
- Mesothelin expression in gynecologic carcinosarcoma: clinicopathological significance and correlation with HER2 expression.Journal of gynecologic oncology · 2024Article
- Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells.Oncology reports · 2022Article
- The Network of Cytokines in Brain Metastases.Cancers · 2021Review
- Targeting Neoepitopes to Treat Solid Malignancies: Immunosurgery.Frontiers in immunology · 2021Review
- GPI-AP: Unraveling a New Class of Malignancy Mediators and Potential Immunotherapy Targets.Frontiers in oncology · 2020Review
- 5-Azacytidine Potentiates Anti-tumor Immunity in a Model of Pancreatic Ductal Adenocarcinoma.Frontiers in immunology · 2020Article
- The role of the immune system in brain metastasis.Current neurobiology · 2019Article
- Adaptive hypofractionated gamma knife radiosurgery in the acute management of brainstem metastases.Surgical neurology international · 2019Article
- Epstein-Barr virus- and cytomegalovirus-specific immune response in patients with brain cancer.Journal of translational medicine · 2018Article
- Mesothelin-Specific Immune Responses and Targeted Immunotherapy for Mesothelin-Expressing Tumors.EBioMedicine · 2017Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with advanced malignancies, e.g. lung cancer, ovarian cancer or melanoma, frequently present with brain metastases. Clinical presentation and disease progression of cancer is in part shaped by the interaction of the immune system with malignant cells. Antigen-targeted immune responses have been implicated in the prolonged survival of patients with cancer. This includes the tumor-associated antigen (TAA) mature mesothelin, a 40kDa cell surface-bound antigen that is overexpressed in several malignancies including lung ovarian and pancreatic cancer. We examined in an observational, prospective study the survival of patients with brain metastases in association with clinical parameters and cellular immune responses to molecularly defined TAAs or viral (control) target antigens.
methodsImmune cells in peripheral blood obtained from thirty-six patients with brain metastases were tested for cytokine production in response to a broad panel of defined viral and TAA target antigens, including full-length mesothelin. Incubation of immune cells with antigenic targets was carried out in i) medium alone, (ii) in a cytokine cocktail of interleukin (IL)-2/IL-15/IL-21, or (iii) IL-2/IL-7. Supernatants were tested for interferon gamma (IFN-γ) production, after which univariate and multivariate analyses (Cox stepwise regression model) were performed to identify independent clinical and immunological factors associated with patient survival. Patients were followed-up for at least 500days after surgery or until death.
findingsUnivariate analysis identified age, gender, radiotherapy and mutational load as clinical parameters affecting survival of patients with brain metastases. Cox multivariate analysis showed that radiotherapy (P=0·004), age (P=0·029) and IFN-γ responses to mature mesothelin, conditioned by IL-2/IL-7 (P=0·045) were independent predictors of the survival of patients from surgery up to follow-up or death.
interpretationThis is the first evidence that immune responses to mesothelin serve as a marker of increased overall survival in patients with brain metastases, regardless of the primary tumor origin. Analyses of immunological markers could potentially serve as prognostic markers in patients with brain metastases and help to select patients in need for adjunct, immunological, treatment strategies.
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