The changes of immunologic properties and their prognostic implications: the paired analysis of initial and recurrent head and neck squamous-cell carcinoma

Abstract

Purpose The immunologic properties of tumors can change during the clinical course. We aimed to compare the expression of PD-L1 and the infiltration of CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment between initial and recurrent head and neck squamous-cell carcinomas (HNSCCs). We also evaluated whether the changes of those immunologic properties in recurrent HNSCCs affect the oncologic outcome. Methods We included 42 patients who had been treated for both initial and recurrent HNSCCs. Pathologic specimens from initial and salvage surgery were obtained for each patient, and IHC staining of CD3, CD8, PD-1, and PD-L1 were done. Also, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were collected. The change of each immunologic profile was expressed as the recurrent-to-initial ratio (R/I ratio). Results The change of CD3+, CD8+, PD-1, and PD-L1 positive cells varied widely. For more than half the patients, those values decreased in recurrent tumors. The median R/I ratio was 0.5 for CD3+ TILs, 0.6 for CD8+ TILs, 0.5 for PD-1 and 0.4 for PD-L1. In contrast, NLR and PLR increased in recurrent tumors for more than half the patients. The median R/I ratio of NLR and PLR was 1.6 and 1.4, respectively. In multivariate analysis, increased CD8 (R/I ratio >1) was the independent prognostic factor for better OS (hazard ratio 0.228; 95% CI 0.067 – 0.777; p= 0.018). Conclusion The change of immunologic properties along with the recurrence of HNSCC varied widely from patient to patient. Generally, the intratumoral biomarkers decreased, while the systemic inflammatory markers increased. The increased CD8+ TILs in recurrent HNSCCs was the significant prognostic factor for better overall survival.