Here, we established a novel syngeneic OSCC model derived from a 4NQO-induced OSCC in the tongue that showed similarities with HPV-negative HNSCC by recapitulating mutations seen in human tumors, constitutive transforming growth factor beta (TGFβ) signaling, abundant TIL in TNC-rich stroma, and spontaneous tumor cell dissemination to the local lymph nodes. Here, TGFB1 is linked to head and neck squamous cell carcinoma.