Microwave ablation of non-small cell lung cancer enhances local T-cell abundance and alters monocyte interactions.

Abstract

Background: Minimally invasive thermal therapies show great prospect in non-small cell lung cancer (NSCLC) treatment. However, changes in immune cell populations following microwave ablation (MWA) in NSCLC microenvironment are not fully revealed.

Objective: The present study was conducted to identify changes in immune cell populations and analyse dysregulated genes in immune cells after MWA in NSCLC microenvironment.

Methods: The patients received fractionated MWA in two treatments separated by 3 weeks. Tumor biopsy samples were obtained through core-needle biopsy before each fractionated MWA procedure at the same site and used for single-cell RNA sequencing with the 10x Genomics pipeline.

Results: A total of 9 major cell types were identified after MWA, which include neutrophils, T cells, B cells, monocytes, epithelial cells, chondrocytes, macrophages, tissue stem cells, and endothelial cells. After MWA, the tumor tissue exhibited an increased proportion of T cells. MWA altered gene expression in each cell cluster at the single-cell level. Cell trajectory analysis revealed that the cells at the starting point were most like T helper cells, naïve T cells, and regulatory T cells; they then developed into anergic T cells, T follicular cells, natural killer T cells, T memory cells, and exhausted T cells, and finally ended as γδ T cells and cytotoxic T cells. Moreover, after MWA, more interaction between monocytes and T cells (or B cells) were identified.

Conclusions: MWA increases local T-cell abundance and alters monocyte interactions, thereby reshaping the tumor microenvironment. This study lays a foundation for investigating dysregulated genes that may contribute to the MWA-induced immune response in NSCLC.

What is already known on this topic: Thermal ablation may change the immune profiles of patients by activating various steps in the cancer immunity cycle. However, changes in immune cell populations following MWA of NSCLC have not been fully reported.

What this study adds: After MWA, an increase in interactions between monocytes and T cells intratumorally was observed, which promoted antitumor immunity.

How this study might affect research, practice or policy: The current study illuminates the MWA-caused systemic immune response in NSCLC, which may help to identify the dysregulated genes involved in the MWA-caused immune response.