Proteomics analysis explored the changes in the tumor microenvironment of CT26 tumor-bearing mice after microwave ablation.

Background: Microwave ablation (MWA) effectively generates large high-temperature ablation zones. This modality achieves direct tumor destruction while stimulating antitumor immunity and potentially inducing abscopal effects, though with limited systemic efficacy. Emerging evidence suggests post-MWA tumor microenvironment (TME) modifications critically influence immune activation, yet the underlying mechanisms remain poorly understood. Notably, localized proteomic changes in the TME following MWA require comprehensive characterization to elucidate its immunomodulatory properties.

Aim of the study: This study investigates proteomic changes in TME after MWA to identify critical protein signatures modulating antitumor immunity.

Material and methods: This study utilized a Balb/c murine model with subcutaneous CT26 cell injections to assess MWA effects on the TME. MWA treatment (5 w-3 min) was administered using a microwave generator, followed by LC-MS analysis using a tims TOF Pro with gradient elution and parallel accumulation serial fragmentation data collection. Protein expression differences were analyzed via t-test and further interpreted with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway bioinformatics.

Results: MWA induced substantial proteomic changes, with 545 upregulated and 678 downregulated proteins compared to controls. Integrated bioinformatics analysis demonstrated significant alterations in biological processes, cellular components, and molecular functions, particularly enriched in tumor cell growth-related pathways. Protein interaction network analysis identified pivotal hub proteins such as cap-binding protein subunit 1 (NCBP1) and cell division cycle 5-like protein (CDC5L) potentially mediating cellular responses to MWA treatment.

Conclusion: MWA significantly induced protein alterations in TME, with NCBP1 and CDC5L standing out as promising candidate targets for tumor treatment.