Details

Autor(en) / Beteiligte

• Shafi, Saba
• Aung, Thazin Nwe
• Robbins, Charles
• Zugazagoitia, Jon
• Vathiotis, Ioannis
• Gavrielatou, Niki
• Yaghoobi, Vesal
• Fernandez, Aileen
• Niu, Shuqiong
• Liu, Linda N.
• Cusumano, Zachary T.
• Leelatian, Nalin
• Cole, Kimberley
• Wang, He
• Homer, Robert
• Herbst, Roy S.
• Langermann, Sol
• Rimm, David L.

Titel

Development of an immunohistochemical assay for Siglec-15

Ist Teil von

• Laboratory investigation, 2022-07, Vol.102 (7), p.771-778

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Siglec-15, a member of sialic-acid binding immunoglobulin type lectins, is normally expressed by myeloid cells and upregulated in some human cancers and represents a promising new target for immunotherapy. While PD-L1 blockade is an important strategy for immunotherapy, its effectiveness is limited. The expression of Siglec-15 has been demonstrated to be predominantly mutually exclusive to PD-L1 in certain cancer histologies. Thus, there is significant opportunity for Siglec-15 as an immunotherapeutic target for patients that do not respond to PD-1/PD-L1 inhibition. The aim of this study was to prospectively develop an immunohistochemical (IHC) assay for Siglec-15 to be used as a companion diagnostic for future clinical trials. Here, we create and validate an IHC assay with a novel recombinant antibody to the cytoplasmic domain of Siglec-15. To find an enriched target, this antibody was first used in a quantitative fluorescence (QIF) assay to screen a broad range of tumor histologies to determine tumor types where Siglec-15 demonstrated high expression. Based on this and previous data, we focused on development of a chromogenic IHC assay for lung cancer. Then we developed a scoring system for this assay that has high concordance amongst pathologist readers. We then use this chromogenic IHC assay to test the expression of Siglec-15 in two cohorts of NSCLC. We found that this assay shows a higher level of staining in both tumor and immune cells compared to previous QIF assays utilizing a polyclonal antibody. However, similar to that study, only a small percentage of positive Siglec-15 cases showed high expression for PD-L1. This validated assay for Siglec-15 expression may support development of a companion diagnostic assay to enrich for patients expressing the Siglec-15 target for therapy.