Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.

Pleural Fluid Has Pro-Growth Biological Properties Which Enable Cancer Cell Proliferation

“…The protocol used for cancer cell culture is described elsewhere (16). When pleural fluid was used as culture medium in the experiments, mostly fresh pleural fluid (kept in refrigerator at 3-4°C for up to 3 days) was used, but when this was not available, freshly-thawed-from-frozen unfiltered pleural fluid samples were used.…”

“…Patient-derived cancer cell cultures are a faithful laboratory model with the potency to recapitulate the biology of the disease (13)(14)(15). Patient-derived MPM cancer cell cultures from MPE samples reflect tumor and patient heterogeneity and closely resemble native tumor specimens (16). There is a need to further understand the role of pleural fluid.…”

Establishment and Characterization of Patient-Derived Xenografts (PDXs) of Different Histology from Malignant Pleural Mesothelioma Patients

“…MPMs are relatively rare, aggressive tumors for which new therapeutic strategies are particularly warranted due to the very poor prognosis these patients have [15][16][17][18][19][20][21]. Data obtained so far with immunotherapy (in particular with the use of immune checkpoint inhibitors) were below the expectancies [7,[22][23][24][25][26], particularly when we consider that their use vastly improves the outcome in other tumor types [27][28][29][30][31]. One of the factors limiting the discovery of new drugs and/or combinations potentially active in MPM is the scarce availability of models able to recapitulate the malignancy.…”

“…One of the factors limiting the discovery of new drugs and/or combinations potentially active in MPM is the scarce availability of models able to recapitulate the malignancy. In fact, there were several cell lines isolated from patients with MPM whose growth in vitro and response was evaluated in different laboratories [ 1 , 31 , 32 ], and some of these were also grown as organoids in 3D [ 31 , 32 , 33 ]. We demonstrated that the in vitro response in cells growing in monolayer does not always reflect the situation in more complex systems.…”

Use of preclinical models for malignant pleural mesothelioma

“…The majority of available malignant cell lines can be passaged indefinitely. As such, genomic instability, including polyploidy, 64 copy number alterations and the emergence of new aberrations 58 74 have been observed following long-term culture of MPM models. Moreover, kataegis, the accumulation of a large number of single nucleotide substitutions clustered in a single locus was reported in MPM cell cultures but not primary tumour tissue.…”