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. 2025 Aug;47(8):2114-2122.
doi: 10.1002/hed.28128. Epub 2025 Mar 5.

Combined Tumor Infiltrating Lymphocytes and PD-L1 Status in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Catherine T Haring  1 , Joshua D Smith  2 , Sarah M Dermody  2 , Jonathan B McHugh  3 , William R Perry  3 , Collin Brummel  2 , Matthew E Spector  4 , J Chad Brenner  2 , Paul L Swiecicki  5
Affiliations

Combined Tumor Infiltrating Lymphocytes and PD-L1 Status in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Catherine T Haring et al. Head Neck. 2025 Aug.

Abstract

Objectives: To determine if the assessment of CD8+ tumor-infiltrating lymphocytes (TILs) adds prognostic information to the PD-L1 combined positive score (CPS) in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Methods: A retrospective case series was performed of 77 patients with R/M HNSCC between 2003 and 2019. From pre-treatment biopsies, CD8+ TILs and PD-L1 CPS were quantified on a tissue microarray. Associations of biomarkers with overall survival and immune checkpoint inhibition (ICI) response were assessed.

Results: Neither CD8+ TIL counts nor PD-L1 CPS alone were associated with overall survival; however, combined high TILs and CPS ≥ 1 were associated with improved survival compared to low TILS and CPS < 1 (18.5 vs. 10.0 months, p = 0.058). For patients treated with ICI (n = 28), PD-L1 CPS predicted ICI response more strongly than CD8+ TILs.

Conclusions: In R/M HNSCC, the combination of PD-L1 CPS and CD8+ TILs is a stronger prognostic biomarker for overall survival compared with either biomarker alone.

Keywords: biomarkers; human papillomavirus viruses; immune checkpoint inhibitors; squamous cell carcinoma of head and neck; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Representative samples of CD8‐stained tumor biopsies. The tumor on the left was classified as having high CD8+ TILs, whereas the tumor on the right was classified as having low CD8+ TILs. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Overall survival for the cohort when classified by both CD8+ TILs and PD‐L1 CPS. Patients with high TILs + CPS ≥ 1 had longer mOS compared to those with low TILs and CPS < 1 (18.5 months vs. 10.0 months, p = 0.058). [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
ICI treatment response did not differ by CD8+ TILs (a) but did differ by PD‐L1 CPS (b). Patients with CPS ≥ 1 were more likely to have a good response to treatment compared to those with CPS < 1. Combining CD8 + TILs with PD‐L1 CPS did not improve the predictive potential of PD‐L1 CPS alone (c).
See this image and copyright information in PMC

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