PRDM1 Is Associated with Chemoradiotherapy-Associated Enrichment of Adaptive NK Cells in Cervical Cancer

Chemoradiotherapy (CRT) induces tumor cell death and remodeling of the tumor immune microenvironment. Adaptive natural killer (aNK) cells, initially characterized in chronic viral infection, are now recognized as important in solid tumors, contributing to antitumor immunity and immune memory. However, the dynamics of aNK cell response to CRT and the regulatory mechanisms behind their activation are not well understood. We analyzed single-cell RNA sequencing data from cervical cancer patients before CRT, after the first CRT fraction, and after the second fraction. We found that CRT markedly enriched aNK cells, with increased cytotoxicity and enhanced virus-defending programs. Among the differentially expressed genes, the transcription factor PRDM1 (PR/SET domain 1, also known as BLIMP-1:B lymphocyte-induced maturation protein 1) was consistently up-regulated in aNK cells after both rounds of CRT. To explore the potential role of PRDM1, we performed in silico perturbation analyses using scTenifoldKnk and CellOracle. These computational simulations predicted reduced effector-associated programs and perturbed metabolic networks following PRDM1 disruption in aNK cells. Moreover, PRDM1 perturbation altered inferred cellular trajectories, opposing the transcriptional shift toward an adaptive NK-associated state, suggesting that PRDM1 may contribute to maintenance of aNK-associated identity and functional features in the CRT-conditioned tumor microenvironment. These findings identify PRDM1 as a candidate regulator associated with aNK cell enrichment, activation-related remodeling, and trajectory-associated changes following CRT, providing insight into immune remodeling during CRT and highlighting PRDM1 as a promising regulatory candidate for future investigation in radiotherapy-induced antitumor immunity.