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

J Oral Pathol Med. 2024 Mar;53(3):217-225. doi: 10.1111/jop.13525. Epub 2024 Mar 6.

Abstract

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.

Keywords: PD-L1; immune checkpoint blockade; odontogenic carcinoma; tumor immune microenvironment.

MeSH terms

  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor
  • CD8-Positive T-Lymphocytes / pathology
  • Carcinoma* / pathology
  • Forkhead Transcription Factors
  • Humans
  • Immune Checkpoint Inhibitors
  • Mouth Neoplasms* / pathology
  • Odontogenic Tumors* / pathology
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors
  • Forkhead Transcription Factors
  • Biomarkers, Tumor