Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer

• Published in: Laboratory investigation Vol. 102; no. 10; p. 1143
• Main Authors: Shafi, Saba, Aung, Thazin Nwe, Xirou, Vasiliki, Gavrielatou, Niki, Vathiotis, Ioannis A, Fernandez, Aileen, Moutafi, Myrto, Yaghoobi, Vesal, Herbst, Roy S, Liu, Linda N, Langermann, Sol, Rimm, David L
• Format: Journal Article
• Language: English
• Published: United States 01.10.2022
• Subjects: B7-H1 Antigen - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Head and Neck Neoplasms; Humans; Lung - metabolism; Lung Neoplasms - pathology; Programmed Cell Death 1 Receptor; Sialic Acid Binding Immunoglobulin-like Lectins - therapeutic use; Squamous Cell Carcinoma of Head and Neck; Urinary Bladder Neoplasms
• ISSN: 1530-0307

Immune checkpoint blockade with programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has resulted in significant progress in the treatment of various cancer types. However, not all patients respond to PD-1/PD-L1 blockade, underscoring the importance of identifying new potential targets for immunotherapy. One promising target is the immune system modulator Siglec-15. In this study, we assess Siglec-15 expression in solid tumors, with a focus on lung, breast, head and neck squamous and bladder cancers. Using quantitative immunofluorescence (QIF) with a previously validated antibody, we found increased Siglec-15 expression in both tumor and immune cells in all the four cancer types. Siglec-15 was seen to be predominantly expressed by the stromal immune cells (83% in lung, 70.1% in breast, 95.2% in head and neck squamous cell and 89% in bladder cancers). Considerable intra-tumoral heterogeneity was noted across cancer types. As previously described for non-small cell lung cancer (NSCLC), Siglec-15 expression was seen to be mutually exclusive to PD-L1 in all the four cancer types, although this differential expression was maintained but somewhat diminished in head and neck squamous cell carcinoma (HNSCC). Siglec-15 was not prognostic either for overall survival (OS) or progression-free survival (PFS). In summary, we show broad expression of this potential immune modulatory target in a wide range of cancer types. These data suggest potential future clinical trials in these tumor types.