As an added layer of complexity, a surge in the circulating levels of ICD-associated biomarkers such as high mobility group box 1 (HMGB1), which has been correlated with improved disease outcome in patients with breast carcinoma or HNSCC receiving ICD-inducing agents [152, 153], may de facto originate from ICD-unrelated processes, hence potentially being poorly predictive of a positive interaction with ICIs. The gene discussed is HMGB1; the disease is head and neck squamous cell carcinoma.