Tumor immune microenvironment in odontogenic carcinomas: Evaluation of the therapeutic potential of immune checkpoint blockade

• Published in: Journal of oral pathology & medicine Vol. 53; no. 3; pp. 217 - 225
• Main Authors: Oh, Kyu‐Young, Hong, Seong‐Doo, Yoon, Hye‐Jung
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.03.2024
• Subjects: Cancer; Carcinoma; CD3 antigen; CD8 antigen; Foxp3 protein; immune checkpoint blockade; Immune checkpoint inhibitors; Immunohistochemistry; Inflammation; Lymphocytes; Lymphocytes T; Malignancy; Microenvironments; odontogenic carcinoma; PD-L1 protein; PD‐L1; Spatial distribution; tumor immune microenvironment; Tumors; PD-L1; tumor immune microenvironment; odontogenic carcinoma; immune checkpoint blockade
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.13525

Background Despite recent advances in the use of immune checkpoint blockade (ICB) across various cancer types, its efficacy in odontogenic carcinomas remains unexplored. This study aims to investigate PD‐L1 expression and the tumor immune microenvironment (TIME) in odontogenic carcinomas to determine the therapeutic potential of ICB and the significance of immune markers. Methods The expressions of PD‐L1 and T cell markers (CD3, CD8, and FOXP3) were visualized by immunohistochemistry in 21 tissue samples of odontogenic carcinomas. Tumoral PD‐L1 expression and the density and spatial distribution of T cell subsets were evaluated, from which TIME was determined. The associations of the variables with clinicopathological and prognostic factors were statistically analyzed. Results PD‐L1 was positively expressed in 52.4% (11/21) of the cases studied. Among tumor types, ameloblastic carcinoma showed significantly higher PD‐L1 expression (p = 0.016). TIME based on the intratumoral and stromal T cell distribution was immune‐inflamed in 61.9% (13/21) and immune‐excluded in 38.1% (8/21), with no immune‐desert cases. PD‐L1 expression was associated with the densities of all intratumoral T cell subsets (p = 0.03 for CD3, p = 0.03 for CD8, and p = 0.008 for FOXP3) but not with those of stromal T cells. High PD‐L1 expression was associated with larger tumor size (p = 0.021), while the intratumoral CD8/CD3 ratio was inversely correlated with tumor size (p = 0.048). Conclusion These findings indicate the involvement of adaptive immune resistance in a subset of odontogenic carcinomas and support the therapeutic potential of ICB in patients with these rare malignancies.