Work

Multi-omic paired analysis reveals chemotherapy-associated immunosuppressive changes and therapeutic insights in recurrent endometrial carcinoma

Year: 2026

Type: article

Abstract: Combination chemotherapy with immune checkpoint blockade has reshaped the treatment landscape for recurrent endometrial carcinoma (EC). However, subgroup analyses have demonstrated limited efficacy in patients previously treated with platinum-based adjuvant chemotherapy. To investigate how prior adjuvant chemotherapy affects the tumor microenvironment (TME) at recurrence, we analyzed 32 matched primary–recurrent EC pairs by performing multi-omic profiling in 20 pairs and multiplex immunohistochemistry (mIHC) in all cases. Recurrent tumors with prior platinum-based adjuvant chemotherapy exhibited increased variant allele frequencies of mutations in MYC signaling-related genes, with enrichment of glycolysis, regulatory T (Treg) cells, and M2 macrophage polarization. mIHC demonstrated increased Treg-cell infiltration and the M2/M1 macrophage ratio in recurrent tumors compared with matched primary tumors. Moreover, progression-free survival after recurrence correlated more strongly with the TME of recurrent tumors than with that of the primary tumors. Platinum-based adjuvant chemotherapy is associated with the emergence of immunosuppressive TME features in recurrent EC.

Source: npj Precision Oncology

DOI: 10.1038/s41698-026-01668-8