86 Extensive FAP expression analysis in 23 tumor indications and potential application in defining the patient population in FAP-targeting cancer immunotherapies

Background Fibroblast activation protein alpha (FAP) is frequently over-expressed in the tumor microenvironment (TME) while exhibiting limited expression normal tissues. FAP was reported to be immunosuppressive mouse models and generally associated with worse prognosis clinical studies. Therefore, it important understand context which both exhibits characteristics a useful target for immunotherapy. Methods Comprehensive immunohistochemistry (IHC) analyses on formalin-fixed paraffin-embedded tissue specimens emphasis lymph nodes primary metastatic lesions spanning wide range of indications were undertaken this study. staining tissues performed an optimized IHC robust-prototype-assay (RPA) manually scored. The area (normal stroma & neoplastic) positively relative total at each intensity level recorded H-score calculated (FAP-intensity score).These supplemented by gene analysis using public as well Roche phase 1, 2 3 cancer immunotherapy (CIT) trial data sets. Results Analysing confirmed general absence apart from subset pancreatic islet cells. Unlike more homogenous typical targets cells, TME heterogeneous pattern intensity, requiring large sample set. we evaluated 1216 samples 23 70 sub-indications. exhibited significant spread ranging highly abundant those low coverage.Using matching mRNA significantly correlate RPA H-scores (Spearman correlation: 0.62) (N=289, P=1.2E-31). Gene 12 atezolizumab studies, including standard care (SOC) randomized than 6000 4 major interrogated association between response overall progression free survival. This suggests that higher hazard ratios across all atezolizumab-treated (OS: 95% CI 1.04–1.09; PFS: 1.04–1.08), highest effect observed Renal Cell Carcinoma 1.08–1.31; 1.05–1.21), indicating potential role limiting CIT. Conclusions Data these can tailor indication patient enrichment strategies achieving optimal FAP-targeting. We propose select FAP-levels are high enough enable drug accumulation, yet reduce effects hamper successful