PD-L1 Expression and Tumor-infiltrating Lymphocytes in Uterine Smooth Muscle Tumors: Implications for Immunotherapy

• Published in: The American journal of surgical pathology Vol. 43; no. 6; p. 792
• Main Authors: Shanes, Elisheva D, Friedman, Lisa A, Mills, Anne M
• Format: Journal Article
• Language: English
• Published: United States 01.06.2019
• Subjects: Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase - analysis; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - analysis; Biomarkers, Tumor - analysis; Female; Humans; Immunotherapy; Leiomyoma - drug therapy; Leiomyoma - immunology; Leiomyoma - pathology; Leiomyosarcoma - drug therapy; Leiomyosarcoma - immunology; Leiomyosarcoma - pathology; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Middle Aged; Prognosis; Smooth Muscle Tumor - drug therapy; Smooth Muscle Tumor - immunology; Smooth Muscle Tumor - pathology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - pathology; Uterine Neoplasms - drug therapy; Uterine Neoplasms - immunology; Uterine Neoplasms - pathology; Young Adult
• DOI: 10.1097/PAS.0000000000001254

Immunotherapies targeting the PD-1/PD-L1 checkpoint axis are of growing interest for the treatment of mesenchymal neoplasms. However, PD-L1 expression and tumor-associated lymphocytes have not been well-investigated in uterine smooth muscle tumors. Forty-nine uterine smooth muscle tumors (23 leiomyosarcomas, 8 smooth muscle tumors of uncertain malignant potential [STUMP], 7 atypical leiomyomas, and 11 benign leiomyomas) were evaluated for tumoral and tumor-associated immune PD-L1 expression and tumor-associated T-cell infiltration. ALK immunohistochemistry was performed to exclude inflammatory myofibroblastic tumors. Tumor PD-L1 expression was seen in 70% of leiomyosarcomas and 14% of atypical leiomyomas; no cases of STUMP or benign leiomyoma demonstrated tumoral PD-L1. PD-L1 positivity was seen in tumor-associated immune cells in 78% of leiomyosarcomas, 25% of STUMP, no cases of atypical leiomyomas, and 9% of benign leiomyomas. Of the 23 leiomyosarcomas, 15 (65%) had a combined positive score ≥1, while of the 26 other uterine smooth muscle tumors, only 2 (8%) had a combined positive score ≥1. Tumor-associated CD8+ cells were highest among leiomyosarcomas (mean: 87/high-power fields vs. 17/high-power fields for nonleiomyosarcomas), and were significantly associated with PD-L1 expression. One PD-L1, CD8-enriched leiomyosarcoma showed an ALK overexpression suggesting possible classification as inflammatory myofibroblastic tumor, but otherwise lacked morphologic features of this entity. Leiomyosarcomas demonstrate significantly higher PD-L1 expression and cytotoxic T-cell infiltration when compared with other uterine smooth muscle tumors. These data suggest the possibility that treatment with targeted immunotherapy may be appropriate in a selected population of patients with leiomyosarcoma and, potentially, in related tumors bearing ALK rearrangements.