Work

P1290: a Tissue-based Ex Vivo Culture System to Anticipate Tehrapy Response in Lymphoma.

Year: 2022

Type: article

Abstract: Background: B-cell malignancies are a heterogenous group of malignancies that acquire multiple genomic alterations over time and in which the interactions between tumor cells and the tumor microenvironment (TME) are often important for tumor growth. Modeling lymphoma ex vivo has been hampered by the lack of suitable 3D models and the complexity of translating organoid technology from other cancer types into lymphoma. Hence, research mainly relies on the use of transgenic and xenograft animal models. Aims: We wanted to develop a method to maintain lymphoma tissue explants in culture which could be used to study lymphoma pathogenesis and to test response to anti-cancer therapies directly on patient tumor tissues. We call these tumor tissue fragments lymphomoids. Methods: We have designed an ex vivo culture system to maintain lymphoma tissues in culture for several weeks. We have tested this technology on murine models of lymphoma and on tissue biopsies obtained from 9 different patients diagnosed with different lymphoma subtypes. To confirm that our method supports tissue architecture for several weeks we have performed multiparametric FACS analyses, single-cell RNA sequencing, high-plex spatial proteomics profiling, and spatial transcriptomics analyses. Results: With our approach, we are able to preserve the tissue composition and the interactions between tumor cells and their microenvironment ex vivo for three to four weeks. The transcriptional profile of tumor tissue biopsies was highly conserved in lymphomoids, indicating that we are able to maintain the tissue heterogeneity present in the original tumors. To anticipate sensitivity to anti-cancer therapies, we have tested and compared response to targeted therapies and immunotherapy on lymphomoids obtained from the 9 human primary lymphomas. Histopathological and spatial transcriptomic analyses showed patient-specific sensitivity to particular compounds and revealed features on the tumor tissue composition associated with resistance or response to therapies. Summary/Conclusion: Overall, we have developed a system to maintain patient-derived lymphomoids in culture which allows to anticipate sensitivity and resistance to anti-cancer therapies, and it could potentially be used to identify the best therapeutic options for each patient in a clinical setting.

Source: HemaSphere

DOI: 10.1097/01.hs9.0000848024.58707.55