• TLS are emerging biomarkers of ICI response in HNSCC. • TLS density correlates with improved ICI response and survival outcomes. • TLS within 100 µm of the tumour boundary predict enhanced ICI response. • Mature TLS in HPV+ OPSCC correlate with prolonged progression-free survival. Head and neck squamous cell carcinoma (HNSCC) is the seventh most prevalent cancer diagnosed in Australia, accounting for significant morbidity and mortality. Locoregional recurrence occurs in approximately half of HNSCC patients. Immunotherapy response rates in HNSCC remain modest at 20–35%. Therefore, it is essential to review and build on the evidence around how immunotherapy response is shaped by the tumour microenvironment (TME). Tertiary lymphoid structures (TLS) are emerging as predictors of immunotherapy response. This review summarises recent studies on TLS in HNSCC and investigates whether these have potential as predictive biomarkers.
Griffin et al. (2026) studied this question.