Due to the promising potential of HLA-G blockade, ongoing researches about why and how HLA-G-based therapeutic approaches quell the malignant phenotype are increasing, as exemplified by the deciphering of the roles of HLA-G positive cancer cells in colorectal cancer using spatial and single-cell transcriptomics [10], and the employment of HLA-G-targeted CAR-T cells for the direct killing of EGFR-mutated and overexpressed oral cancers [11]. The gene discussed is HLA-G; the disease is lip and oral cavity carcinoma.