On the basis of this, we generated the immunocompetent combined Tgfbr1/Pten conditional knockout (2cKO) mouse model by crossing K14-CreERtam; Tgfbr1flox/flox (Tgfbr1 cKO) mice with Ptenflox/flox mice, which spontaneously develops HNSCC with full penetration, and is suitable for preclinical intervention, especially for cancer immunotherapy research [29]. Here, PTEN is linked to cancer.