Abstract 1625: Distribution and prevalence of LAG-3 expression in samples of melanoma and gastric/gastroesophageal junction cancer
Authors: Dillon Lloye M. , Wojcik John , Desai Keyur , Lei Ming , Johnson Lori , McCune Bryan , Johnson Krystal , Shuster Jeffrey , Anderson Steven M. , Li Bin 
Published: July 2021

Background: Immune checkpoint inhibitors (ICIs) have become the standard of care in a range of tumors. However, a large proportion of patients treated with ICIs have treatment-refractory/resistant tumors requiring innovative approaches. Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint receptor that inhibits effector T-cell function. Preclinical data suggest that simultaneous activation of the LAG-3 and programmed death-1 pathways results in greater T-cell exhaustion than either pathway alone, leading to impaired antitumor immune response and increased tumor growth. Therefore, LAG-3 may be a promising new target for cancer immunotherapy. The objective of this study was to assess the distribution of LAG-3 expression on lymphocytes in melanoma, gastric cancer (GC), and gastroesophageal junction cancer (GEJC) samples using an immunohistochemistry (IHC) assay.

Methods: Formalin-fixed, paraffin-embedded samples from resected melanoma, GC, or GEJC ≤ 5 years old were procured for analysis. The LAG-3 IHC assay was developed and performed by LabCorp (Research Triangle Park, NC) using the anti-LAG-3 17B4 mouse antibody clone on a Leica Bond III platform. LAG-3 expression was assessed as the percentage of positive immune cells (ICs) within the invasive margin, tumor, and stroma. Programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) and ICs was evaluated on the same samples using the Dako PD-L1 IHC 28-8 pharmDx assay to determine the percentage of PD-L1-expressing TCs and the combined positive score (CPS).

Results: A total of 102 melanoma samples, 256 GC samples, and 84 GEJC samples were included in this study. LAG-3 expression was detected in the majority of samples across all tumor types, with higher expression in GEJC than in melanoma or GC. LAG-3 prevalence was similar across subgroups based on disease stage (melanoma, GC) and grade (GC). LAG-3 prevalence was also consistent across subgroups based on age, sex, and ethnicity (all tumor types), as well as alcohol consumption and smoking history (melanoma and GC). LAG-3 expression was weakly correlated with PD-L1 expression on TCs (Spearman's ρ of 0.31 for GC, 0.41 for GEJC, and 0.46 for melanoma) and moderately correlated with PD-L1 CPS (Spearman's ρ of 0.63 for GC and 0.73 for GEJC). Similar correlations were observed after binning PD-L1 TC score and CPS.

Conclusions: LAG-3-expressing lymphocytes were identified in all tumor types tested. LAG-3 expression did not differ with age, sex, ethnicity, alcohol consumption, and smoking history, and appeared to be associated, but not strongly correlated, with PD-L1 expression in all tumor types. PD-L1 and LAG-3 expression in procured samples may not be reflective of expression observed in clinical trials, and further studies are needed to characterize LAG-3 expression in a clinical setting.

Citation Format: Lloye M. Dillon, John Wojcik, Keyur Desai, Ming Lei, Lori Johnson, Bryan McCune, Krystal Johnson, Jeffrey Shuster, Steven M. Anderson, Bin Li. Distribution and prevalence of LAG-3 expression in samples of melanoma and gastric/gastroesophageal junction cancer [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 1625.