Abstract

Background: Leukocytes in peripheral blood (PB) are prognostic biomarkers in head and neck squamous cell carcinoma cancer patients (HNSCC-CPs), but differences between HNSCC-CPs and healthy adults (HAs) are insufficiently described. Methods: 10-color flow cytometry (FCM) was used for in-depth immunophenotyping of PB samples of 963 HAs and 101 therapy-naïve HNSCC-CPs. Absolute (AbsCC) and relative cell counts (RelCC) of leukocyte subsets were determined. A training cohort (TC) of 43 HNSCC-CPs and 43 HAs, propensity score (PS)-matched according to age, sex, alcohol, and smoking, was used to develop a score consecutively approved in a validation cohort (VC). Results: Differences in AbsCC were detected in leukocyte subsets (p < 0.001), but had low power in discriminating HNSCC-CPs and HAs. Consequently, RelCC of nine leukocyte subsets in the TC were used to calculate 36 ratios; receiver operating characteristic (ROC) curves defined optimum cut-off values. Binary classified data were combined in a score based on four ratios: monocytes-to-granulocytes (MGR), classical monocytes-to-monocytes (clMMR), monocytes-to-lymphocytes (MLR), and monocytes-to-T-lymphocytes (MTLR); ≥3 points accurately discriminate HNSCC-CPs and HAs in the PS-matched TC (p = 2.97 × 10−17), the VC (p = 4.404 × 10−178), and both combined (p = 7.74 × 10−199). Conclusions: RelCC of leukocyte subsets in PB of HNSCC-CPs differ significantly from those of HAs. A score based on MGR, clMMR, MLR, and MTLR allows for accurate discrimination.

Highlights

  • Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor in the world [1,2]

  • A recent study showed the frequency of CD14+ CD16− human leukocyte antigen (HLA)-DRhigh monocytes to be a strong predictor of progression-free (PFS) as well as overall survival (OS) in response to anti-PD-1 immunotherapy with the immune-checkpoint inhibitor; a clear response to the treatment was shown in the T-cell compartment [11]

  • In-depth immunophenotyping of peripheral blood samples of healthy adults (HAs) and therapy-naïve HNSCC-CPs using 10-color flow cytometry identifies the strongest differences in relative cell counts of monocytes, classical monocytes, lymphocytes, and T-lymphocytes

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Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor in the world [1,2]. Several studies investigated the absolute (AbsCC) and relative cell count (RelCC) and the change in leukocyte subsets that occurred in association with the disease. As these subsets are known to play a key role in immune surveillance and anti-tumor immune responses, which are dependent on the effective cooperation of monocyte-derived antigen-presenting cells (APC) in the stimulation of cytotoxic (Tc, CD3+ CD8+ ). HNSCC-CPs. Absolute (AbsCC) and relative cell counts (RelCC) of leukocyte subsets were determined. Conclusions: RelCC of leukocyte subsets in PB of HNSCC-CPs differ significantly from those of HAs. A score based on MGR, clMMR, MLR, and MTLR allows for accurate discrimination

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