Abstract 3679: PD-L1 driven excluded phenotype in melanoma

Abstract

Abstract Background: The excluded phenotype has been previously described by the presence of abundant immune cells that do not penetrate the parenchyma of these tumors but instead are retained in the stroma that surrounds nests of tumor cells. These features support a pre-existing anti-tumor immune-related response, but the details of this mechanism are not well elucidated. Methods: 300 formalin-fixed, paraffin-embedded (FFPE) metastatic cutaneous melanoma samples were evaluated by the RNA-seq component of a comprehensive immune profile panel to measure transcript levels of immune-related genes. Resultant data was QC filtered, normalized and ranked based on an assorted reference population of various tumor types. The expression of PD-L1 on the surface of tumor cells was assessed in tumor samples by means of an automated IHC assay (28-8, Dako). A tumor was considered PD-L1 positive if ≥1% of viable tumor cells exhibited complete circumferential or partial linear plasma membrane staining at any intensity. Excluded pattern of T-cell infiltration was defined by CD8 immunohistochemistry by the following definition: Restriction of more than 95% of all CD8+ T-cells present in a tumor to the periphery or interstitial stromal areas and not actively invading nest or groups of neoplastic cells. Results: The excluded phenotype was identified in 34 of 300 (11%). PD-L1 by IHC was positive (≥1%) in the neoplastic cases in 16 of 34 (47%) cases. Membranous staining in immune cells was identified in only 3 of 34 (9%) cases, but was present in >90% of all cases in a non-membranous pattern. In more than one-half of all cases the non-membranous pattern of PD-L1 IHC staining was restricted to the excluded TILs. Higher expression of PD-L1 by RNA-seq was associated with this excluded PD-L1 pattern of staining. Conclusion: In 300 metastatic cutaneous melanoma cases we demonstrated that the excluded phenotype is frequent and represents ~10% of all cases. Moreover, in a significant number of excluded cases expression of PD-L1 by IHC was distinctly limited to the excluded TILs. This finding would support a unique mechanism of PD-L1 anti-tumor immune-related response that needs further investigation. Citation Format: Carl Morrison, Jeffrey Conroy, Mary Nesline, Sean Glenn, Blake Burgher, Maochun Qin, Jonathan Andreas, Vincent Giamo, Felicia L. Lenzo, Angela Omilian, Wiam Bshara, Antonios Papanicolau-Sengos, Yirong Wang, Marc Ernstoff, Mark Gardner, Sarabjot Pabla. PD-L1 driven excluded phenotype in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3679.