Immunotherapy response modeling by ex-vivo organ culture for lung cancer.

摘要: One of the major hurdles for advancement cancer immunotherapy is lack robust, accessible experimental models. We aimed to produce an ex-vivo organ culture (EVOC) model non-small cell lung (NSCLC). Freshly resected early stage tumors were collected from operating room, fragmented clusters < 450 µm and cultured with fetal calf serum human autologous serum. The resulting EVOC includes epithelial cells within tumor tissue clusters immune cells. Original features are reflected in EVOCs. response checkpoint inhibitors (ICI) was assessed by IFNγ gene induction. Interestingly, induction numerically higher when anti-CTLA4 added anti-PD-L1 treatment, supporting notion that impacts partly through tumor-resident In parallel, immunohistochemistry (IHC) key immune-related proteins performed on formalin-fixed paraffin embedded (FFPE) corresponding tumors. ICI correlated basal non-induced IFNγ, CD8, CD4 FOXP3 mRNA levels EVOCs tumor-FFPE-IHC CD8 granzyme B. A weaker correlation seen CD3, CD4, CD68, tumor-PD-L1. Tertiary lymphoid structure density also response. Our study provides novel data about biomarkers correlate ICI-induced NSCLC. Retention microenvironment minimal addition exogenous factors suggest this reliably represent original tumor. cluster-based we describe can provide a valuable, yet simple widely applicable tool