Jia Zeng

Immune Subtypes and Immune Landscape Analysis of Endometrial Carcinoma

Abstract Some patients with endometrial cancer (EC) suffer from limited survival benefits after immunotherapy, suggesting that there may be a specific pattern associated with immunotherapy. Immune-related genes were extracted from The Cancer Genome Atlas databases. We analyzed the differences among immune subtypes (ISs) in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, immune checkpoint-related genes, immunotherapy, and chemotherapy. We applied dimensionality reduction and defined the immune landscape of EC. Then, we used the Weighted Gene Co-Expression Network Analysis package to identify the coexpression modules of these immune genes. Finally, hub genes were selected and detected by quantitative PCR and immunohistochemistry. We obtained three ISs. There were differences in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, and immune checkpoint–related genes among the ISs. Regarding immunotherapy and chemotherapy, the IS2 subtypes were more sensitive to programmed cell death protein 1 inhibitors. In addition, different positions in the immune landscape map exhibited different prognostic characteristics, providing further evidence of the ISs. The IS2 subtypes were significantly positively correlated with yellow module gene list, indicating a good prognosis with high score. SIRPG and SLAMF1 were identified as the final characteristic genes. The quantitative PCR and immunohistochemistry results showed that the expression levels of SIRPG and SLAMF1 were low in human EC tissue. In this study, we identified three reproducible ISs of EC. The immune landscape analysis further revealed the intraclass heterogeneity of the ISs. SIRPG and SLAMF1 were identified to be associated with progression, suggesting that they may be novel immune-related biomarkers of EC.

Effect of prior adjuvant radiotherapy on immunotherapy outcomes in recurrent endometrial cancer

This study aimed to investigate the impact of adjuvant external beam radiotherapy (EBRT) following initial surgery on the efficacy of immunotherapy in patients with recurrent endometrial cancer. This is a single-institution retrospective cohort study. Patients who underwent initial surgery for endometrial cancer and received immunotherapy for recurrence between January 2020 and December 2023 were recruited. Patients who received post-operative EBRT were assigned to the EBRT group. Patients who did not undergo EBRT or who received brachytherapy without EBRT were assigned to the control group. Progression-free survival was used as the end point. Kaplan-Meier curves were used for comparing progression-free survival. The multi-variate analysis was performed using the Cox proportional hazards regression model. A total of 91 patients were included in the analysis; 33 had a history of EBRT, while 58 had not received prior EBRT. In Kaplan-Meier curves, patients who did not receive EBRT showed a numerically lower risk of disease progression (HR 0.47, 95% CI 0.25 to 0.90, p = .010). In multi-variate analysis, EBRT (HR 5.28, 95% CI 1.54 to 22.06) and proficient mismatch repair/micro-satellite instability-low/micro-satellite stable status (HR 3.15, 95% CI 1.19 to 8.90) were risk factors for disease progression during immunotherapy. In patients with recurrent endometrial cancer who received immunotherapy, the therapeutic efficacy may be compromised by prior post-operative adjuvant EBRT.