Uterine leiomyosarcomas (Ut-LMSs) are rare smooth muscle tumors accounting for approximately 1% of patients with uterine malignant tumor with an estimated annual incidence of 0.64 per 100,000 women. Ut-LMS are considered neoplasms of high metastatic potential with 5-year overall survival rates varying between 0 and 73%. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of Ut-LMS is not substantially correlated with hormonal conditions, and the risk factors of Ut-LMS are not clearly understood. The presentation of antigenic peptides by major histocompatibility complex (MHC) class I molecules is important for tumor rejection by cytotoxic T-lymphocytes (CTLs). Such antigenic peptides are generated as a result of the degradation of intracellular proteins by the ubiquitin proteasome pathway, a process that is influenced by the interferon (IFN)--inducible proteasome beta-subunit (PSMB)9/1i, which is -subunit of the 20S proteasome. Homozygous deficient mice for PSMB9/1i are now known to spontaneously develop Ut-LMS. Expression of PSMB9/1i is reportedly absent in human UtLMS, but present in human myometrium. Further studies revealed a few infiltrating CD56bright natural killer (NK) cells, which are known as "uterine NK cells" (uNK cells), in human Ut-LMS tissues. This short communication aims at summarizing recent insights into the regulation of NK cell function and the T lymphocyte-mediated immune system as tumor immune surveillance in the female genital system