Abstract 4038: In-depth PD-L1 scoring reveals potential correlations between tumor-intrinsic PD-L1 and myeloid-inflamed profiles in head and neck cancer
Authors: Tsujikawa Takahiro , Kawaguchi Tsutomu , Yoshimura Kanako , Mitsuda Junichi , Aarai Akihito , Hirano Shigeru 
Published: August 2019

Abstract
Programmed cell death protein-1 (PD-1) inhibition has been showing encouraging results for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), which simultaneously requires the development of predictive biomarkers to guide selection of conventional and immune checkpoint therapies. Most recently, PD-L1 IHC scoring of tumor and inflammatory cells, but not of tumor cells alone, has been reported as effective metrics for selection between PD-1 inhibition and standard combination therapy of platinum/5-FU/cetuximab for HNSCC. Toward establishment of PD-L1 score-based biomarkers, the present study is aimed to evaluate in-depth PD-L1 profiles of tumor and immune cells in association with immune complexity profiles of HPV-positive and negative HNSCC via 12-marker multiplex immunohistochemistry (IHC) and image cytometry. As previously reported (Tsujikawa et al. Cell Reports. 2017), oropharyngeal HNSCC cases were divided into three clusters of lymphoid-, hypo-, and myeloid-inflamed profiles based on cell densities of immune cell lineages. Averages of PD-L1+ percentages in immune cells were 5.3, 7.1, and 12.8 in lymphoid-, hypo-, myeloid-inflamed groups, respectively. High PD-L1 expression on immune cells was observed in CD163+CSF1R+ tumor-associated macrophages and mature dendritic cell populations particularly in intra-tumor regions. Interestingly, averages of PD-L1+ percentages in tumor cells were 0.17, 0.64, and 5.3 in lymphoid-, hypo-, myeloid-inflamed groups, respectively, suggesting that tumor-intrinsic PD-L1 expression without lymphoid-inflamed profiles was potentially associated with myeloid-inflamed profiles. To further evaluate the prognostic significance of PD-L1 expression with low lymphoid-inflamed profiles, we evaluated the the Cancer Genome Atlas (TCGA) HNSCC cohort (N = 528), and observed that high PD-L1 expression with low CD8+ T cell cytolytic activity was associated with short overall survival. Immune complexity analysis for longitudinal specimens from a nivolumab-resistant case with PD-L1 expression on tumor cells revealed the potential involvement of myeloid-inflamed status, suggesting the presence of differential PD-L1 profiles between tumor and immune cells in the context of lymphoid/myeloid-inflamed status. Those findings together indicate that combination of in-depth PD-L1 scoring and immune complexity profiling may contribute to biomarker development toward optimized management for HNSCC.Acknowledgement: This project was supported by the Japan Society for the Promotion of Science Grant-in-Aid (17H07016).
Citation Format: Takahiro Tsujikawa, Tsutomu Kawaguchi, Kanako Yoshimura, Junichi Mitsuda, Akihito Aarai, Shigeru Hirano. In-depth PD-L1 scoring reveals potential correlations between tumor-intrinsic PD-L1 and myeloid-inflamed profiles in head and neck 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 4038.