Immune Checkpoint Markers in Superficial Angiosarcomas: PD-L1, PD-1, CD8, LAG-3, and Tumor-Infiltrating Lymphocytes. (August 2021)

• Record Type: Journal Article
• Authors: Googe, Paul B.; Flores, Kyle; Jenkins, Francie; Merritt, Bradley; Moschos, Stergios J.; Grilley-Olson, Juneko E.
• Is Part Of: American journal of dermatopathology. Volume 43:Number 8(2021)
• Publication Date: 2021-08
• Subjects: angiosarcoma -- PD-L1 -- PD1 -- LAG-3 -- tumor-infiltrating lymphocytes -- immunohistochemistry -- immune checkpoint markers; Skin -- Diseases -- Periodicals; Histology, Pathological -- Periodicals; 616.50705
• DOI: 10.1097/DAD.0000000000001843
• Languages: English
• ISSNs: 0193-1091

Abstract

Abstract : Abstract: Cutaneous angiosarcomas may express programmed death ligand-1 (PD-L1) and PD-L1 expression, and the presence of tumor-infiltrating lymphocytes (TILs) correlates with outcome. These observations provide a basis for PD-1/PD-L1 inhibitor therapy. Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that interacts with the PD-L1 axis and is considered to be a marker of immune exhaustion. The presence of LAG-3–positive lymphocytes in cutaneous angiosarcoma has not been established. We reviewed 10 cases of treatment naive angiosarcoma of skin and superficial soft tissue and assessed for PD-L1 (ZR3) expression, presence of TILs, and expression of CD8, PD1, and LAG-3 by tumor-associated inflammatory cells by immunohistochemistry. All 10 angiosarcomas were positive for PD-L1: 7 with high expression and 3 with low expression. TILs were present in all tumors: brisk in 7 and nonbrisk in 3. CD8 lymphocytes were present in all tumors with a range of 212–1274 cells per square millimeter (mean 557 CD8 cells/mm 2 ). LAG-3–positive lymphocytes were present in 9 of 10 angiosarcomas with a range of 0–728 cells/mm 2 (mean 146 LAG-3 cells cells/mm 2 ). The ratio of LAG-3 lymphocytes to CD8 lymphocytes was 0%–59% (mean 27%). The PD1 cell counts were intermediate between CD8 and LAG3 counts. Cutaneous angiosarcomas frequently express PD-L1, have prominent numbers of CD8 positive, and have smaller numbers of LAG-3–positive and PD-1–positive TILs. Our findings provide further evidence of PD-L1 expression in cutaneous angiosarcoma and the promise for immune checkpoint inhibitor therapy.