The prognostic role of NK cells and their ligands in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis

Sangeeta K Bisheshar, Emma J. de Ruiter, Lot A Devriese, Stefan M. Willems

Research output: Contribution to journalArticleAcademicpeer-review

38 Citations (Scopus)
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Background: Despite the improvement in therapeutic interventions, 5-year survival rates in Head and Neck Squamous Cell Carcinoma (HNSCC) are limited. HNSCC is an immunogenic cancer type for which molecular stratification markers are lacking. Tumor-infiltrating lymphocytes (TILs) have shown a favorable prognostic role in different cancer types. This study focused on the prognostic role of NK cells in HNSCC.

Methods: A systematic search was conducted in Pubmed/Medline and Embase. Articles that correlated the presence of intratumoral NK cells, activating/inhibiting receptors, death receptors, or their ligands with clinicopathologic characteristics or survival were included. A meta-analysis was performed that assessed the association between CD56+ and CD57+ and overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS).

Results: A pooled analysis indicated a favorable prognostic role of CD56+ and CD57+ NK cells for OS (HR 0.19 CI 0.11–0.35). NK cell markers NKp46 and Granzyme B (GrB) also have a favorable prognostic role. NK cell ligand Fas correlated with better survival and better characteristics. NK cell marker Fas-L, NK cell ligands CEACAM1, RCAS1, CD70 and TRAIL-R, and effector molecules of these ligands, FADD and FAP1, correlated to features of worse prognosis.

Conclusion: A favorable prognostic role of NK cells in HNSCC was found in this review. Some studies implied the opposite, indicating the fine balance between pro- and anti-tumor functions of NK cells. Future studies using homogeneous patient cohorts regarding tumor subsite and treatment modality, are necessary to further provide insight into the prognostic role of NK cells.
Original languageEnglish
Article numbere1747345
Pages (from-to)1-10
Number of pages10
Issue number1
Publication statusPublished - 23-Apr-2020
Externally publishedYes


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