The prognostic role of tumor associated macrophages in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis

Sangeeta K Bisheshar; Martine F van der Kamp; Emma J de Ruiter; Lilian N Ruiter; Bert van der Vegt; Gerben E Breimer; Stefan M Willems

doi:10.1016/j.oraloncology.2022.106227

The prognostic role of tumor associated macrophages in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis

Oral Oncol. 2022 Dec:135:106227. doi: 10.1016/j.oraloncology.2022.106227. Epub 2022 Nov 3.

Authors

Sangeeta K Bisheshar¹, Martine F van der Kamp², Emma J de Ruiter³, Lilian N Ruiter⁴, Bert van der Vegt⁵, Gerben E Breimer⁶, Stefan M Willems⁷

Affiliations

¹ Department Pathology and Medical Biology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands; Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Electronic address: [email protected].
² Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands. Electronic address: [email protected].
³ Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Electronic address: [email protected].
⁴ Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Electronic address: [email protected].
⁵ Department Pathology and Medical Biology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands. Electronic address: [email protected].
⁶ Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Electronic address: [email protected].
⁷ Department Pathology and Medical Biology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands. Electronic address: [email protected].

PMID: 36335818
DOI: 10.1016/j.oraloncology.2022.106227

Abstract

Head and neck squamous cell carcinoma (HNSCC) is an immunogenic cancer type, and tumor associated macrophages (TAMs) are a major component of the tumor microenvironment (TME). In this systematic review and meta-analysis, studies assessing tumor infiltration with CD68+, iNOS+, HLA-DR+, CD11b+, CD163+, CD206+, and CD204+TAMs were included, and correlation to survival hazard was studied. A low number of CD68+TAMs correlated to better overall survival (OS) in multivariate analysis (HR 1.36 95 %CI (1.07-1.72) P = .01). CD68+TAMs did not correlate to disease free survival (DFS), disease specific survival (DSS), progression free survival (PFS), or recurrence free survival (RFS). A low number of CD163+TAMs correlated to better OS in uni- and multivariate analysis (resp. HR 2.65 95 %CI (1.57-4.46) P = .01 and HR 2.42 95 %CI (1.72-3.41) P < .001). A low number of CD163+TAMs also correlated to better DFS and PFS, whereas a low number of CD204+TAMs only correlated to PFS. While IHC analysis of pan macrophage marker CD68 and M2-like marker CD163 both show prognostic utility in OS, CD163 is a stronger prognosticator, as indicated by multivariate meta-analysis. CD163+TAMs also correlate to DFS and PFS; outcomes that are more relevant to patients, thus showing promising results for future clinical implementation.

Keywords: CD163; CD204; CD206; CD68; Disease free survival (DFS); Disease specific survival (DSS); Head and Neck Squamous Cell Carcinoma (HNSCC); Locoregional control (LRC); Overall survival (OS); Progression free survival (PFS); Recurrence free survival (RFS); Tumor associated macrophages (TAMs).

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Antigens, Differentiation, Myelomonocytic / metabolism
Head and Neck Neoplasms*
Humans
Prognosis
Squamous Cell Carcinoma of Head and Neck
Tumor Microenvironment
Tumor-Associated Macrophages*

Substances

Antigens, Differentiation, Myelomonocytic