Patient-Derived Explant Cultures (PDECs) as a Model System for Immuno-Oncology Studies

Abstract

Abstract Background To address current need for preclinical human-based immuno-oncology models, we have established a method to grow 3D cultures of intact fragments of patient-derived breast cancer tissue; Patient-Derived Explant Cultures (PDECs). PDECs offer many advantages over other cancer model systems. For example, PDECs preserve the human tumor microenvironment, reflect inter- and intra-patient tumor heterogeneity and results are obtained within one week. Up to 16 samples can be obtained from one clinical sample, allowing the same ‘patient’ to be experimentally treated with different drug regimens and/or measurement of more than one endpoint. Recently we have used PDECs to assess the efficacy of novel synthetic lethal treatment regimens (Haikala et al., Nature Comm. 2019; Tervonen et al., Oncogene 2016). Methods To assess whether PDECs are also a suitable model for IO studies we performed immunoprofiling experiments with FACS, RT-PCR and immunofluorescence of PDECs and the primary tumor they were derived from. Results These experiments showed that the immune-contexture, i.e. the number and activation status of different immune cell types, is similar in PDECs than in the primary tumor. In addition, using serial cell imaging we found that activation of resident immune cells in PDECs using anti-PD-1 (an immune checkpoint inhibitor) or Immunocult (T Cell Activator) resulted in shrinkage of some PDECs, while others were unaffected. In addition, the presence of increased levels of cancer cell death in PDECs treated with anti-PD-1 and Immunocult suggests that the resident immune cells in PDECs can mediate cancer cell killing. Conclusion Our data support our hypothesis that PDECs retain a similar immunocontexture as the original tumors, and can be interrogated with immunomodulatory compounds relevant to current immunotherapies. Legal entity responsible for the study The authors. Funding Academy of Finland, Juselius Foundation, Cancer Organisations. Disclosure All authors have declared no conflicts of interest.