Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Simona Corso, Marilisa Cargnelutti, Stefania Durando, Silvia Menegon, Maria Apicella, Cristina Migliore, Tania Capeloa, Stefano Ughetto, Claudio Isella, Enzo Medico, Andrea Bertotti, Francesco Sassi, Ivana Sarotto, Laura Casorzo, Alberto Pisacane, Monica Mangioni, Antonino Sottile, Maurizio Degiuli, Uberto Fumagalli, Giovanni Sgroi, Sarah Molfino, Giovanni De Manzoni, Riccardo Rosati, Michele De Simone, Daniele Marrelli, Luca Saragoni, Stefano Rausei, Giovanni Pallabazzer, Franco Roviello, Paola Cassoni, Anna Sapino, Adam Bass, Silvia Giordano
Patient-Derived Xenografts (PDXs), entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer.More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV) positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted.Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment.Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples.



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