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• W2896783280 abstract "The poliovirus receptor (PVR) is an immune checkpoint protein expressed on tumor cells. It has been reported to mediate activation of T cells via CD226 or inhibition through binding to T-cell Ig and ITIM domain (TIGIT). TIGIT competes with CD226 for binding to PVR, and exhibits stronger affinity for PVR. Recently we have found that PVR is highly expressed in SCLC cell lines. Characterizing the expression and significance of the PVR-TIGIT axis in SCLC will help us to better understand the immunology of SCLC and may lead to novel therapeutic strategies to combine checkpoint blocking agents for improved SCLC immunotherapy. Immunohistochemistry (IHC) was performed to evaluate PVR protein expression in a TMA of 39 SCLC cell lines and a cohort TMA of 77 limited stage SCLC patients with clinical data. We analyzed both PVR and TIGIT in an independent cohort of 27 resected, limited-stage SCLC tumors. Thirty-seven cell lines (95%, 37/39) demonstrated staining for PVR and of those, 4 cell lines (10.3%, 4/39) showed strong staining (H-score ≥ 270). In the 77 SCLC patients cohort, PVR expressed predominantly in the membrane of tumor cells, with minimal expression observed on immune cells. PVR expression in the SCLC patient cohort was 82% with an arbitrary H-score cut-off of ≥ 50. Higher PVR expression was found for male patients (P=0.040). The expression of PVR increased with the tumor progressing from stage I to stage III (p =0.007). SCLC patients who had higher PVR expression demonstrated poorer prognosis and the difference was near statistically significant (p=0.050). Using the same cut-off (H-score ≥ 50) in the independent SCLC cohort, the prevalence of high PVR expression was 89% (24/27). In the independent SCLC cohort, TIGIT was found to be expressed membranous or cytoplasm on the immune cells with weak to moderate staining. Immune cells with TIGIT staining were typically seen as variable size and aggregated toward the periphery of the tumor nest. TIGIT protein staining was demonstrated in 20 cases (74%). No association was found between PVR H-score and TIGIT expression by Fisher’s test (p=0.093). PVR is broadly expressed in SCLC cell lines and tumor tissues. The expression of TIGIT protein was also found in SCLC patients with weak to moderate staining. Blockade of the PVR-TIGIT pathway may represent a possible future target to immunotherapy in SCLC patients." @default.
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• W2896783280 date "2018-10-01" @default.
• W2896783280 modified "2023-10-14" @default.
• W2896783280 title "P3.12-13 Expression of the Immune Checkpoint Axis-PVR/TIGIT in Small Cell Lung Cancer" @default.
• W2896783280 doi "https://doi.org/10.1016/j.jtho.2018.08.1836" @default.
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