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In a clinical trial (NCT02919683) of patients with head and neck squamous cell carcinomas of the oral cavity, neoadjuvant anti-PD1 or anti-PD-1/anti-CTLA4 treatment promoted the expansion of anti-cancer CD8+ T cell clones that did not exist in the tumors before the treatment (197), suggesting that these newly generated anti-cancer CD8+ T cells are derived from the TDLNs and not from the expansion of pre-existing exhausted CD8+ T cells in the tumor