Single-Cell Profiling of the Immune Atlas of Tumor-Infiltrating Lymphocytes in Endometrial Carcinoma

SIMPLE SUMMARY: Immunotherapy has a unique potential for improving various types of cancer treatment. However, related studies in endometrial carcinoma are lacking. Further studies on the tumor-infiltrating lymphocyte populations are vital. We firstly mapped the immune atlas of lymphocytes in type I endometrial carcinoma via single-cell RNA sequencing, mass cytometry and flow cytometry analysis. Three transcriptionally distinct NK cell subsets with different antitumor functions were identified. Some CD103+ CD8+ T cells were also defined as tissue-resident memory T cells in endometrial carcinoma. Both our retrospective study and analysis of a public repository suggest the correlation between antitumor function of CD103+ CD8+ T cells and EC prognosis. Certain key molecular mechanisms potentially determining the phenotypes of NK cells and CD103+ CD8+ T cells were highlighted and might serve as novel therapeutic targets. ABSTRACT: Endometrial carcinoma (EC) is a gynecological malignancy with a high incidence; however, thorough studies on tumor-infiltrating lymphocyte (TIL) populations in EC are lacking. We aimed to map the immune atlas of TILs in type I EC via single-cell RNA sequencing (scRNA-seq), mass cytometry and flow cytometry analysis. We found that natural killer (NK) cells and CD8+ T lymphocytes were the major components of TILs in EC patients. We first identified three transcriptionally distinct NK cell subsets, which are likely to possess diverse anti-tumor functions. Additionally, CD103+ cells substantially contributed to the CD8+ T cell population. The signature gene expression of CD103+ CD8+ T cells indicated the tissue residency, immunological memory, and exhaustion properties of this cell subset, which were defined as tissue-resident memory T cells (T(RM) cells). Moreover, based on scRNA-seq and mass cytometry analysis, we first identified the intrinsic heterogeneity of CD103+ CD8+ T cells that were thought to have a distinct cytotoxicity, cell adhesion and exhaustion status functions. Collectively, distinct subsets of NK cells were found and might shed light on future investigations. CD103+ CD8+ T cell population may be an important immunotherapeutic target in EC and targeting this cell population with combined immunosuppressive therapy might improve the efficacy of immunotherapy for EC.