Table 1.
Comparison of human ‘en bloc’ patient-derived organoid/patient-derived explant models
| Model | Patient-derived organotypic tumor spheroids | Air-liquid interface patient-derived organoids | Ex vivo organ culture | Patient-derived tumor fragments |
|---|---|---|---|---|
| Culture type | Submerged in collagen matrix with microfluidics | Air-liquid interface | Submerged in medium | Submerged in collagen-Matrigel matrix |
| Tissue fragmentation | Mincing, filtration (100 μM and 40 μM filters) | Mincing | Manual dissection, followed by mechanical and enzymatical dissociation, filtration (450 μm filter) | Manual dissection |
| Size | 40-100 μm | 40-100 μm | 30-450 μm | 1-2 mm |
| Culture time | 6 days | >1 month | 5 days | 2 days |
| Medium supplements | NA | 50% Wnt3a, RSPO1, Noggin, nicotinamide, N-acetylcysteine, B-27 without vitamin A, A83-01, gastrin, SB-202190, EGF | Transferrin-insulin-selenium mix, amphotericin, gentamycin, non-essential amino acids | Non-essential amino acids, sodium pyruvate |
| Maintenance of cancer morphology | Yes | Yes | Yes | NA |
| Maintenance of immune infiltrate | Yes | Yes | Yes | Yes |
| Maintenance of immune organization | NA | NA | NA | Yes |
| Type of ICB tested | Anti-PD-1, anti-CTLA-4, anti-PD-1 + anti-CTLA-4 | Anti-PD-1 | Anti-PD-L1, anti-PD-L1 + anti-CTLA-4 | Anti-PD-1 |
| Characterization of ICB response | Broad cytokine and chemokine profiling RNAseq |
RT-PCR (IFN-γ, granzyme B, perforin) | RT-PCR (IFN-γ), IHC (granzyme B) | Broad cytokine and chemokine profiling Flow cytometry |
| Perturbation | NA | NA | NA | Inhibition of TCR signaling and IFN-γ signaling |
CTLA-4, cytotoxic T lymphocyte-associated protein 4; ICB, immune checkpoint blockade; IFN, interferon; NA, no data available; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; RNAseq, RNA sequencing; TCR, T-cell receptor.