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• W2995252012 abstract "Abstract Background Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases, and is characterized by a poor response to chemotherapy and a low survival rate. Treatment targeting the immune checkpoint inhibitor pathway PD-1/PD-L1 has been found to be effective against NSCLC with manageable side effects, but with only 20-25% of patients showing a positive response there is an urgent need for additional immunotherapy options for this group of patients. LAG-3 and PD-1 are often co-expressed and upregulated on T cells leading to immune exhaustion and tumor growth, and co-blockade of the LAG-3 and PD-1 pathways has been shown to synergize to improve T cytotoxic cell responses. Methods In order to perform a comprehensive immunoprofiling of NSCLC tumors we used MultiOmyx™, an immunofluorescence (IF) multiplexing assay that utilize a pair of directly conjugated Cyanine dye-labeled (Cy3, Cy5) antibodies per round of staining. Using a 16-marker panel we have analyzed the proportion of B cells, T cell subtypes, M1/M2-type tumor-associated macrophages, as well as the expression of PD-1, PD-L1, LAG-3, and TIM-3 in 20 samples from patients with NSCLC. Results LAG-3 was found to be expressed mainly on T cytotoxic cells in both subtypes, but the overall density of LAG-3 was 59% higher in squamous cell carcinoma (SCC) tumors compared to adenocarcinoma tumors. In both SCC and adenocarcinoma subtypes TIM-3 was found primarily on tumor-associated macrophages (TAMs), followed by an equal distribution on helper and cytotoxic T cells. When analyzing the proportion of T cytotoxic cells infiltrating into the tumor area, we observed an apparent synergy between LAG-3 and PD-1, suggesting a therapeutic benefit of dual checkpoint blockade of LAG-3 and PD-1 in NSCLC. Conclusion It is our hope that these data will help provide new insights into the biology of NSCLC that can ultimately be used to explore novel immunotherapeutic interventions for lung cancer treatment. Legal entity responsible for the study NeoGenomics. Funding NeoGenomics. Disclosure A. Juncker-Jensen: Full / Part-time employment: NeoGenomics. M. Nagy: Full / Part-time employment: NeoGenomics. J. Kuo: Full / Part-time employment: NeoGenomics. E. Leones: Full / Part-time employment: NeoGenomics. F. Sahafi: Full / Part-time employment: NeoGenomics. K. Pham: Full / Part-time employment: NeoGenomics. E. Parnell: Full / Part-time employment: NeoGenomics." @default.
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• W2995252012 date "2019-12-01" @default.
• W2995252012 modified "2023-10-16" @default.
• W2995252012 title "PD-1 and LAG-3 synergize to drive tumour-infiltration of T cytotoxic cells in NSCLC tumours" @default.
• W2995252012 doi "https://doi.org/10.1093/annonc/mdz452.002" @default.
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