It is intriguing that Duhen et al. (11) report that the presence of stromally located DP CD4+ Th cells was strongly associated with CD39+CD103+CD8+ TIL (known to be enriched for tumor reactivity) content in the TME of HNSCC samples, but did not find such an association in CRC specimens. The gene discussed is CD4; the disease is head and neck squamous cell carcinoma.