The tumor microenvironment of benign and malignant salivary gland tumors

Head Neck. 2024 Jul;46(7):1625-1636. doi: 10.1002/hed.27716. Epub 2024 Mar 7.

Abstract

Background: Treatment of salivary gland tumors (SGTs) remains challenging. Little is known about the immune landscape of SGTs. We aimed to characterize the tumor microenvironment in benign and malignant SGTs.

Methods: Eleven benign and nine malignant tumors were collected from patients undergoing curative intent surgery. Specimens were analyzed using mass cytometry by time-of-flight. Immune cell populations were manually gated, and T cells were clustered using the FlowSOM algorithm. Population frequencies were compared between high-grade and low-grade malignancies, corrected for multiple hypothesis testing.

Results: There were trends towards increased CD4+ and CD8+ T cells among malignant tumors. High-grade malignancies exhibited trends towards higher frequencies of CD8+ PD-1+ CD39+ CD103+ exhausted T cells, CD4+ FoxP3+ TCF-1+ CD127- Tregs, and CD69+ CD25- CD4+ T cells compared to low-grade malignancies.

Conclusion: SGTs exhibit significant immunologic diversity. High-grade malignancies tended to have greater infiltration of exhausted CD8+ T cells and Tregs, which may guide future studies for immunotherapy strategies.

Keywords: CyTOF; immunology; salivary gland cancer; salivary gland tumor; single‐cell.

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Flow Cytometry
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Salivary Gland Neoplasms* / immunology
  • Salivary Gland Neoplasms* / pathology
  • Salivary Gland Neoplasms* / therapy
  • Tumor Microenvironment* / immunology