this study was aimed to investigate the role of lncRNA EGFR-AS1, an antisense transcript of EGFR, in leiomyosarcoma (LMS) and the underling mechanisms.levels of EGFR-AS1 and PD-L1 were measured in LMS tissues and cell lines using qRT-PCR, as well as western blotting and/or immunohistochemical staining; flow cytometry was employed to validate the role of EGFR-AS1 on altering the activity of CD8 + T cells; interaction of EGFR-AS1 and EGFR was determined by fluorescent in situ hybridization (FISH) and RNA pull-down; regulation of MYC on PD-L1 promoter was assessed by chromatin immunoprecipitation (ChIP); a xenograft in vivo tumor growth assay was applied to verify the EGFR-AS1/EGFR/MYC/PD-L1 axis in vivo.up-regulation of EGFR-AS1 and PD-L1 in LMS tissues was negatively correlated with CD8 + T cell infiltration; EGFR-AS1 positively regulated PD-L1, thereby strengthening interaction of LMS cells and CD8 + T cells and triggering CD8 + T cells apoptosis via the PD-1/PD-L1 checkpoint; EGFR-AS1 co-localized and interacted with EGFR to promote MYC activity; MYC was identified as a transcriptional activator of PD-L1.lncRNA EGFR-AS1 was demonstrated to increase PD-L1 expression through the EGFR/MYC pathway in LMS cells, thereby repressing T cell infiltration and contributing to immune escape.© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.