Oral squamous cell carcinoma (OSCC) is one of the most prevalent types of malignancies in the oral cavity, with a high incidence of lymph node (LN) metastasis. While previous studies have explored the mechanisms of lymphatic metastasis, little is known about the cellular architecture within the premetastatic niche of LNs. In this study, we established mouse models of premetastatic LNs, which demonstrated an immunosuppressive premetastatic environment in tumor-draining LNs prior to metastasis. We performed single-cell RNA sequencing on LNs from patients with OSCC, including premetastatic tumor-draining LNs and paired contralateral LNs. Our analysis identified a subset of CD4+ T cells that exclusively expressed