Abstract 2775: PD-L1 expression in human tumors: a tissue microarray study on 5,561 tissue samples and 87 tumor types
Authors: Katharina Möller, Ronald Simon, Martina Kluth, Guido Sauter, Claudia Hube-Magg, Christoph Fraune, Niclas Blessin, Maximilian Lennartz, Doris Höflmayer, Sarah Minner, Eike Burandt, Sören Weidemann, Andreas Luebke
Journal: Cancer Research (2021)

Abstract The programmed death protein 1 (PD-1) and his ligand PD-L1 are frequently expressed in human cancers and immune checkpoint inhibitor therapies targeting the PD1/PD-L1 pathway are increasingly employed in a growing number of tumor types. However, a unanimous picture on PD-L1 expression in cancer cells and immune cells in various cancer types are so far lacking. In this study we analyzed PD-L1 expression in 5,561 tumor samples by immunohistochemistry in a highly standardized way to define the relative importance of PD-L1 expression and its relationship with tumor infiltrating CD8 positive lymphocytes across 87 human tumor types and subtypes. At a cut-off level of 10% positive tumor cells, PD-L1 positivity was seen in 62 of 87 (71%) tumor types. More than 50% PD-L1 positive cases were found in 7 (8%) tumor types, including thymoma (100%), Hodgkin lymphoma (93%), anaplastic thyroid carcinoma (67%), as well as squamous cell carcinomas of the penis (67%), cervix (65%), oral cavity (61%), and pharynx (50%). PD-L1 immunostaining in tumor cells was absent in 25 (29%) tumor types, including non-Hodgkin lymphomas, seminoma, endometrial malignant mixed Müllerian tumors, and mucinous carcinoma of the ovary. In immune cells, PD-L1 positivity was detectable in 79 (91%) tumor types, with the highest positivity rates in tumors of haemotopoetic and lymphoid tissues (75% to 100%), seminoma (85%), Warthin tumors of the parotid glands (83%), and Merkel cell carcinoma (82%). Immune cell PD-L1 positivity was absent in only 8 (9%) tumor types (e.g. chondosarcoma, pleomorphic adenoma of the salivary gland, and chromophobe renal cell carcinoma). PD-L1 positivity in tumor cells was significantly correlated with the number of intratumoral CD8 positive lymphocytes across all tumor types as well as in the separate analyses of several individual tumor types, such as basal cell carcinoma (p&amp;lt;0.0001), chondrosarcoma (p=0.0013), gastrointestinal stromal tumors (p=0.0028), and adrenal cortical carcinoma (p=0.0001). In summary, these data provide a ranking list of tumors according to their PD-L1 positivity rate. The strong association with the frequency of CD8 positive lymphocytes supports the concept, that PD-L1 expression in tumor cells represent a mechanism of highly immunogenic tumors to enable immune evasion. Citation Format: Katharina Möller, Ronald Simon, Martina Kluth, Guido Sauter, Claudia Hube-Magg, Christoph Fraune, Niclas Blessin, Maximilian Lennartz, Doris Höflmayer, Sarah Minner, Eike Burandt, Sören Weidemann, Andreas Luebke. PD-L1 expression in human tumors: a tissue microarray study on 5,561 tissue samples and 87 tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2775.