Abstract

Abstract PD-L1/PD1 immune therapy has been very successful for some patients. Treatment is usually based on PD-L1 tumor expression levels in tumors; however some patients with positive tumors have shown no response to therapy. Recent, clinical trials have shown that treating patients with more than one immune therapy target results in better outcome suggesting the importance of understanding PD-L1 tumor micro environment. In this study, we look at a number of immune cell markers with PD-L1 expression to see if patterns of the immune cells infiltrating the tumor micro environment vary. PD-L1 expression in the tumors was assessed by multiple PD-L1 antibodies since no single PD-L1 antibody has been FDA approved for all tumor types. Immuno-histo chemistry (IHC) screen used 2 recombinant rabbit monoclonal antibodies (clone OR-5E3 and OR-5H8), one mouse anti PD-L1 clone UMAB229, and the FDA approved antibodies clones (SP142 and 28-8). Immune cell markers used in the IHC screen were CD3, CD8A, CD20, CD68, FOXP3, LAG3 and TIM3. The screen was done on sequential sections of bladder, melanoma, and lung tumors. Variation existed between five PD-L1 antibodies in their sensitivity and specificity to detect PD-L1 in the different tumor types; however, the differences were usually associated with the ability to detect low expressing tumors. Immune cell markers CD3, CD8A, CD20, CD68, FOXP3, LAG3, and TIM3 cell markers all produced strong staining if positive cells were present; however, they vary in number and distribution pattern throughout the three types of tumor. For example, when lung or bladder tumors presented strong PD-L1 staining at the edge of the tumor they often had a number of CD3E or CD8A immune positive cells present, this was not the case for CD20 which were foci clusters or scatter through the tumors. FOXP3 and CD68 staining were scarce event in all three tumor types. Although this study was limited to small sample size 10 tumors each it did show differences in the amount and distribution of immune cells in the 3 different types of tumor positive for PD-L1 expression. Citation Format: Rachel Gonzalez, Wei Fu, Evelin Logis, Casey Chen, Tiffany Cone, Sonia Merritt, Yiran Wang, Guanli Wang, Donghui Ma. Immune cell screen of tumor micro environment of PD-L1 in positive/negative bladder cancer, melanoma, and lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 494.

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