Evaluation of tenascin-C by tenatumomab in T-cell non-Hodgkin lymphomas identifies a new target for radioimmunotherapy
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Giuseppe Gritti1, Andrea Gianatti2, Fiorella Petronzelli3, Rita De Santis3, Chiara Pavoni1, Riccardo Lorenzo Rossi4, Laura Cattaneo2, Luigi Giusto Spagnoli5, Silvia Ferrari1, Andrea Rossi1, Anna Maria Barbui1 and Alessandro Rambaldi1,6
1Hematology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy
2Pathology Unit, Ospedale Papa Giovanni XXII, Bergamo, Italy
3Sigma Tau S.p.A. Biotech Products R and D, Pomezia, Italy
4Bioinformatics, Istituto Nazionale Genetica Molecolare, Milan, Italy
5Department of Biomedicine and Prevention, Università di Roma Tor Vergata, Rome, Italy
6Department of Oncology and Oncohematology, Università degli Studi di Milano, Milan, Italy
Alessandro Rambaldi, email: [email protected]
Keywords: T-cell non-Hodgkin lymphoma; peripheral T-cell lymphoma; cutaneous T-cell lymphoma; tenascin-C; radioimmunotherapy
Received: May 13, 2017 Accepted: November 03, 2017 Published: January 03, 2018
The clinical outcome of T-cell non-Hodgkin lymphoma (NHL) is poor and innovative treatments are needed. Tenascin-C is a large extracellular glycoprotein not expressed under physiological conditions, but overexpressed in cancer. Aim of the study was to evaluate tenascin-C expression within pathologic tissue of T-cell NHL and determine its clinical significance. We used an immunohistochemistry approach using the anti-tenascin-C monoclonal antibody Tenatumomab in 75 systemic T-cell NHL (including 72 mature and 3 precursor T-cell NHL), and 25 primary cutaneous T-cell NHL. Data were analyzed in terms of staining intensity, proportion of involved areas and histologic pattern, and results were correlated with clinical characteristics and outcome. Ninety-three percent of the cases were tenascin-C positive and 59% of systemic diseases were characterized by a predominant involvement (>50%). Stromal expression was detected in all the cases while vascular and vascular plus cytoplasmic expression was present in 49% and 23%. The constant overexpression of the tenascin-C gene was observed in two independent publicly available T-cell NHL gene expression datasets. In conclusions, tenascin-C represents an attractive target that sets the rationale to investigate the therapeutic activity of radiolabeled Tenatumomab in T-cell NHL.
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