Immune Cell Infiltrates and Neutrophil-to-Lymphocyte Ratio in Relation to Response to Chemotherapy and Prognosis in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas

Abstract

Our goal was to assess the correlation of immune parameters with the response to induction chemotherapy (ICT) in head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment biopsies from 64 patients with HNSCC that received ICT were assessed for PD-L1 protein expression and density of CD8+ and FOXP3+ tumor infiltrating lymphocytes (TIL). In addition, the neutrophil-to-lymphocyte ratio (NLR) was calculated from pretreatment whole blood counts. In total, 55% of cases exhibited PD-L1 combined proportion score (CPS) positivity (≥1% stained cells). PD-L1 CPS positivity correlated with a high density of both CD8+ (p = 0.01) and FOXP3+ (p < 0.001) TILs. There was no correlation between PD-L1 expression or TIL density and NLR values. In univariate analyses, the absence of PD-L1 CPS expression (p = 0.042) and a high NLR (p = 0.034) were significantly correlated with response to ICT. Neither CD8+ TIL (p = 0.99) nor FOXP3+ TIL densities (p = 0.71) were associated with response to ICT. In multivariate analysis, only a high NLR was associated with response to ICT (HR = 4.06, 95% CI = 1.06–15.5, p = 0.04). In addition, a high NLR was also independently associated with lower disease-specific (p = 0.03) and overall survival rates (p = 0.04), particularly in the subset of patients who received definitive surgical treatment. These results suggest that NLR could emerge as a predictive biomarker of response to ICT.

Predictive Biomarkers for Response and Toxicity of Induction Chemotherapy in Head and Neck Cancers

“…Most of the analyzed immune cell types were also nonsignificant, except CD4 and CD8 lymphocytes and the CD8/FOXP3 ratio, which were higher in the responders ( 52 , 54 ). However, CD4 was analyzed in only one study ( 54 ), while two other studies showed that CD8 and FOX3P alone were not significant ( 32 , 52 ). The remaining parameters were analyzed by individual studies where the responders showed a higher incidence of positive DC-LAMP and PD-1 cells ( 32 ) and a higher lymphocytic host response ( 31 ) while the non-responders were the patients with a higher PD-L1 combined proportion score, an NLR to PD-L1 CPS ratio ( 52 ) and a Brandwein–Gensler risk score ( 31 ).…”

“…The T and N stages, when analyzed separately, were nonsignificant except in ( 14 ) and ( 57 ), where, respectively, a higher T and a higher N were observed in the non-responders. Among the standard laboratory blood parameters, platelet and monocyte counts were not significant, while contradictory results were presented for neutrophil and lymphocyte counts as well as the platelet (PLR) and neutrophil (NLR) to lymphocyte ratios ( 31 , 32 , 52 , 53 ). Most of the analyzed immune cell types were also nonsignificant, except CD4 and CD8 lymphocytes and the CD8/FOXP3 ratio, which were higher in the responders ( 52 , 54 ).…”

“…Among the standard laboratory blood parameters, platelet and monocyte counts were not significant, while contradictory results were presented for neutrophil and lymphocyte counts as well as the platelet (PLR) and neutrophil (NLR) to lymphocyte ratios ( 31 , 32 , 52 , 53 ). Most of the analyzed immune cell types were also nonsignificant, except CD4 and CD8 lymphocytes and the CD8/FOXP3 ratio, which were higher in the responders ( 52 , 54 ). However, CD4 was analyzed in only one study ( 54 ), while two other studies showed that CD8 and FOX3P alone were not significant ( 32 , 52 ).…”

“…Sánchez-Canteli et al. ( 52 ) analyzed the significance of NLR in peripheral blood and the immune infiltrate profiles (i.e., number of CD8+ and FOXP3+ tumor infiltrating lymphocytes (TIL) and programmed cell death ligand 1 (PD-L1) expressions) in the pretreatment biopsies to establish their potential relationship with the response to iCHT. 64 patients (58 men and 6 women) with stage III or IV larynx and hypopharynx SCC were included.…”

“…However, CD4 was analyzed in only one study ( 54 ), while two other studies showed that CD8 and FOX3P alone were not significant ( 32 , 52 ). The remaining parameters were analyzed by individual studies where the responders showed a higher incidence of positive DC-LAMP and PD-1 cells ( 32 ) and a higher lymphocytic host response ( 31 ) while the non-responders were the patients with a higher PD-L1 combined proportion score, an NLR to PD-L1 CPS ratio ( 52 ) and a Brandwein–Gensler risk score ( 31 ). One study reported that the hypopharynx is a favorable localization for iCHT response ( 31 ).…”