An increase of CD8⁺ T cell infiltration following recurrence is a good prognosticator in HNSCC

Programmed death-ligand 1 (PD-L1) expression and CD8-positive tumor-infiltrating lymphocyte (CD8⁺ TIL) infiltration are essential biomarkers for immune checkpoint inhibitor therapy. The objective of this study was to compare the expression of those biomarkers between initial and recurrent HNSCCs using paired analysis. Prognostic significance of those immunological changes was also investigated. Forty-two consecutive patients with locally recurrent HNSCCs were included. Immunohistochemical staining of CD8 and PD-L1 was done for both initial and recurrent tumor specimens. The IHC findings were verified with mRNA expression profiling. Also, the prognostic impact was analyzed based on overall survival (OS). Recurrent-to-initial (R/I) ratios of CD8⁺ TILs and PD-L1 were widely variable. CD8⁺ TIL density and PD-L1 expression decreased in 59.5% and 69% of patients, respectively (R/I ratio < 1). The R/I ratio of CD8A mRNA was significantly higher in patients with a CD8 R/I ratio > 1 (1.7 ± 1.5 vs. 0.6 ± 0.6, p = 0.042). CD8 R/I ratio (> 1) was a good prognosticator for OS (HR 0.293, 95% CI 0.091-0.945, p = 0.040). CD8⁺ TIL infiltration and PD-L1 expression changed variably following local recurrence of HNSCC. The increase of CD8⁺ TILs at recurrence was an excellent independent prognosticator.