Article
Prognostic role of tumor-infiltrating T cells in primary and recurrent meningiomas
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Authors
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Christine Jungk
- Ruprecht-Karls-Universität, Neurochirurgische Klinik, Heidelberg, Deutschland; Universitätsklinikum Heidelberg, Experimentelle Neurochirurgie, Heidelberg, Deutschland
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Matthias Simon
- Evangelisches Klinikum Bethel, Neurochirurgie, Bielefeld, Deutschland; Universitätsklinikum Bonn, Neurochirurgie und Tumorbiologie, Bonn, Deutschland
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Andreas von Deimling
- Deutsches Konsortium für Translationale Krebsforschung (DKTK), Neuropathologie, Heidelberg, Deutschland; Ruprecht-Karls-Universität, Neuropathologie, Heidelberg, Deutschland
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Katrin Lamszus
- Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie und Tumorbiologie, Hamburg, Deutschland
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Ralf Ketter
- Universitätsklinikum des Saarlandes, Klinik für Neurochirurgie, Homburg, Deutschland
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Christel Herold-Mende
- Ruprecht-Karls-Universität, Neurochirurgische Klinik, Heidelberg, Deutschland; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Neuropathologie, Heidelberg, Deutschland; Universitätsklinikum Heidelberg, Experimentelle Neurochirurgie, Heidelberg, Deutschland
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Andreas W. Unterberg
- Ruprecht-Karls-Universität, Neurochirurgische Klinik, Heidelberg, Deutschland
| Published: | June 18, 2018 |
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Outline
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Objective: Meningiomas (MGMs) are the most common primary tumors of the central nervous system. Although aggressive MGMs WHO grade II and III are rare, more effective therapies are urgently needed as reflected by a 5-year-recurrence rate of 50-80% in WHO grade III MGMs despite standard surgical resection and radiotherapy. In the present study we aimed to shed light on the immunological environment in primary (p) and recurrent (r) MGMs to assess a potential suitability of immunotherapeutic approaches.
Methods: We investigated the presence of tumor-infiltrating lymphocytes (TILs) by using a study sample of 202 cases, consisting of 123 pMGMs (n= 33 WHO°I, 64 WHO°II, 26 WHO°III) and 79 rMGMs (n= 10 WHO°I, 33 WHO°II, 36 WHO°III). We quantified levels of TILs in complete tissue sections by multi-colour immunofluorescence stainings of the markers CD3, CD8, FOXP3, and PD-1 by using the semi-automated analysis method TissueFAXS. Univariate and multivariate survival analysis were performed to investigate the influence of TILs on progression-free (PFS) and overall survival (OS) in pMGM patients
Results: We observed a trend towards higher levels of TILs in high-grade pMGMs. Phenotypic sub-classification revealed a higher proportion of infiltrating Thelper cells than cytotoxic Tcells and increasing levels of regulatory T cells along with higher WHO grade. Investigating the impact of TILs on survival, we found a significantly prolonged PFS for pMGM patients with high levels of cytotoxic TILs (p=0.003). We also observed a trend towards aprolonged OS in pMGM patients featuring low levels of regulatory TILs (p=0.066). Comparison of pMGM and rMGM revealed a significantly reduced infiltration of all analyzed TIL phenotypes in rMGM (p<0.01). In addition, we assessed the expression of the T cell co-inhibitory molecule PD-1, which is also a known characteristic feature of antigen-specific Tcells. Here, we identified PD-1+ cytotoxic T cells in the majority of all MGM tissues while high levels of PD-1+ cytotoxic TILs were more frequently found in patients without relapse (p=0.007). Also, high levels of PD-1+ cytotoxic TILs were associated with prolonged PFS (p=0.010) and OS in high-grade pMGM patients (p=0.018).
Conclusion: Our findings demonstrate a distinct phenotypic enrichment of intratumoral T cells in meningiomas, depending on WHO grade and tumor recurrence, and substantiate their prognostic relevance, advocating a future use of immunotherapies in these tumors.
