Table 3 Emerging immunohistochemical biomarkers for checkpoint inhibitor vulnerability.
From: Targeting immune checkpoints in gynecologic cancer: updates & perspectives for pathologists
Biomarker | Function | Ligand(s) | Staining characteristics in the tumoral microenvironment | Clinical trials in gynecologic carcinoma |
|---|---|---|---|---|
LAG-3 | Immunosuppressive checkpoint | MHC Class II, Gal3, LSECtin | Expressed on lymphocytes | NCT03250832 |
TIM-3 | Immunosuppressive checkpoint | Gal9, Cecam-1, HMGB-1, phosphatidyl serine | Expressed on lymphocytes, macrophages, and some tumor cells | NCT03489343; NCT03708328; NCT02817633 |
TIGIT | Immunosuppressive checkpoint | CD112, CD115 | Expressed on lymphocytes | NCT04693234; NCT04570839 |
VISTA | Immunosuppressive checkpoint | VSIG-3, PSGL-1 | Expressed on lymphocytes | NCT04475523 |
CD27 | Immune-activating checkpoint | CD70 | Expressed on lymphocytes, NK cells | NCT02335918 |
CD40 | Immune-activating checkpoint | CD40 Ligand | Expressed on macrophages, dendritic cells | NCT04406623 |
CD134 (OX40) | Immune-activating checkpoint | OX-40 Ligand | Expressed on lymphocytes | NCT01644968; NCT02410512 |
CD137 (4-1BB) | Immune-activating checkpoint | 4-1BB Ligand | Expressed on lymphocytes | NCT02179918; NCT04442126; NCT02410512 |
IDO-1 | Immunosuppressive enzyme | N/A | Expressed on tumor cells, macrophages, other immune cells | NCT03459222; NCT04106414 |
A2AR | Adenosine receptor | Adenosine, GS protein | Expressed on tumor cells, lymphocytes | NCT03629756; NCT03719326 |
CD73 (NT5E) | Immunosuppressive enzyme in the c-AMP pathway | AP-3, SMAD proteins, SP-1 | Expressed on tumor cells, lymphocytes, myeloid-derived suppressor cells | NCT04148937, NCT03255252; NCT03267589 |
MHC class I | Ubiquitous on nucleated human cells; required for adaptive immune recognition and engagement | N/A | Complete membranous expression is normal in nucleated cells; a subset of tumors show complete or subclonal loss | N/A |
