Reducing collagen deposition by inhibiting LOXL2, which promotes crosslinking of ECM proteins and is significantly upregulated in the recurrent HNSCC, maybe a potential approach to activate the exhausted CD8+ T cells in combination with PD-1/PD-L1 blockade immunotherapy as demonstrated recently for lung cancer in a mouse model69. The gene discussed is LOXL2; the disease is head and neck squamous cell carcinoma.