The tumor microenvironment of benign and malignant salivary gland tumors

Katherine C Wai; Trine Line H Okholm; Patrick K Ha; Diana M Marquez; Iliana Tenvooren; Kyle B Jones; Matthew H Spitzer

doi:10.1002/hed.27716

The tumor microenvironment of benign and malignant salivary gland tumors

Head Neck. 2024 Mar 7. doi: 10.1002/hed.27716. Online ahead of print.

Authors

Katherine C Wai^{1

2

3}, Trine Line H Okholm^{1

2

3}, Patrick K Ha^{1

3}, Diana M Marquez^{1

2

3}, Iliana Tenvooren^{1

2

3}, Kyle B Jones^{1

2

3

4

5}, Matthew H Spitzer^{1

2

3

6

7}

Affiliations

¹ Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.
² Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California, USA.
³ Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
⁴ Department of Orofacial Sciences, University of California San Francisco, San Francisco, California, USA.
⁵ Pharma Technical Cell and Gene Therapy, Genentech, Inc., South San Francisco, California, USA.
⁶ Parker Institute for Cancer Immunotherapy, San Francisco, California, USA.
⁷ Chan Zuckerberg Biohub, San Francisco, California, USA.

PMID: 38454566
DOI: 10.1002/hed.27716

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.