CD8⁺ Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: A Review

CD8⁺ tumor-infiltrating lymphocytes (TILs) are increasingly used in oncology as a prognostic and predictive tool to guide patient management. This review summarizes current literature on CD8⁺ TILs in head and neck squamous cell carcinoma (SCC). Published meta-analyses and clinical trials evaluating CD8⁺ TILs were analyzed. Consistent positive associations between elevated CD8⁺ TILs and overall survival have been observed across head and neck sites. CD8⁺ TILs have been found to predict response to treatment, most commonly immunotherapy, but also chemoradiation. Numerous trials have shown that increased CD8⁺ TIL frequencies in pretreatment biopsies could identify patients likely to respond to neoadjuvant therapies. CD8⁺ TIL infiltration has also been elevated in responders both during and after treatment. However, wider adoption of CD8⁺ TIL quantification as a biomarker has been limited by the need for clinical validation and universal measurement guidelines for head and neck SCC, as there are for other malignancies. Measurement variability includes which tumor compartment is sampled, how TILs are quantified, and which cutoffs are clinically relevant. For several head and neck SCC, measurement of CD8⁺ TILs in the central or intratumoral compartment, followed by the stromal compartment, has been most consistently associated with survival. Future studies are needed to evaluate subpopulations of CD8⁺ TILs and biomarker-based treatment selection.