Jeerameth Klomsing

Tumor-infiltrating immune cells and their crosstalk with cancer cells in the tumor microenvironment (TME) play a crucial role in shaping tumor progression and response to therapy. We utilized 3-dimensional liver cancer spheroids incorporating human primary monocytes to investigate the crosstalk between tumor-associated macrophages (TAMs) and Hepatocellular carcinoma (HCC) cells, HepG2 and PLC/PRF/5. Using multiplexed gene expression panels, the critical pathways involved in shaping primary human monocytes to adopt TAMs phenotypes were identified. The specific inhibitor for an identified pathway was used to explore its involvement in polarization of TAMs. In the cocultured spheroids comprising the human HCC cell lines, the infiltrating monocytes resembled protumor M2-like macrophage phenotypes. Gene expression panels of the infiltrating monocytes demonstrated that the upregulated genes were enriched in the cholesterol metabolism pathway. Cholesterol metabolism–related genes were upre...

Trained immunity and tolerance are part of the innate immune memory that allow innate immune cells to differentially respond to a second encounter with stimuli by enhancing or suppressing responses. In trained immunity, treatment of macrophages with β-glucan (BG) facilitates the production of proinflammatory cytokines upon lipopolysaccharide (LPS) stimulation. For the tolerance response, LPS stimulation leads to suppressed inflammatory responses during subsequent LPS exposure. Epigenetic reprogramming plays crucial roles in both phenomena, which are tightly associated with metabolic flux. In this study, we performed a screening of an epigenetics compound library that affects trained immunity or LPS tolerance in macrophages using TNFα as a readout. Among the 181 compounds tested, one compound showed suppressive effects, while 2 compounds showed promoting effects on BG-trained TNFα production. In contrast, various inhibitors targeting Aurora kinase, histone methyltransferase, histone ...