Patient-Derived Organoids of Malignant Pleural Mesothelioma

Background: Malignant Pleural Mesothelioma (MPM) is a relatively rare cancer with an estimated 5-year survival of 9%.

Although precision medicine is the gold standard in medical oncology, reliable biomarkers predicting the treatment response to MPM are still lacking. Therefore, additional preclinical models are needed to identify prognostic and therapeutic biomarkers.

Methods: Patient-derived MPM organoids (PDO-MPMs) were developed through a 3-D culture system from pleural effusion and pleural biopsies of patients with MPM. PDO-MPMs were analysed by H&E staining and immunohistochemistry (IHC) and treated with cisplatin/pemetrexed (Cis/PeMtx) or pembrolizumab (Pemb); response was assessed using TUNEL assay (In Situ Cell Death Detection Kit, Roche, Germany) and expressed as a percentage of dead cells.

Results: Successful PDO-MPM cultures was obtained in 3/6 MPM samples (50%): two PDO-MPMs derived from epithelioid MPM and one from biphasic MPM.

The formed organoids grew as network-like structure, mimicking MPM in vivo (Figure 1A).

PDO-MPMs IHC analysis showed positivity to markers of MPM, as seen in parental tumour (Figure 1B).

Drug response screening to CisPt/PeMtx or to Pemb revealed the PDO-MPM intrinsic resistance, with only 30% of dead cells.

Conclusions: The PDO-MPM could be a promising tool to assess the therapeutic response of approved drugs and to test new potential molecules.