Altered proinflammatory cytokine response in colorectal cancer patientinsights into immune dysregulation

Introduction. Colorectal cancer (CRC) is one of the most common oncological diseases, the patho-genesis of which is closely associated with the development of inflammation. The study of inflammation regulation, including the balance of pro-and antiinflammatory cytokines, is a promising topic for research, allowing for a deeper understanding of the pathogenesis of CRC and improving clinical approaches to the treatment for and diagnosis of this disease. This study investigates the altered secretion of proinflammatory cytokines, i.e., TNF-α and IL-1β, in CRC patients, aiming to elucidate immune dysregulation mechanisms. We sought to investigate the secretion characteristics of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), in patients with CRC. Materials and methods. We enrolled 25 newly diagnosed CRC patients and 20 age-and sex-matched cont-rols. Monocytes were isolated from the peripheral blood of participants using magnetic separation based on the CD14 marker. The isolated monocytes were cultured and subjected to dual stimulation with bacterial lipopolysaccharide at 24 hours and 7 days, followed by quantitative measurement of basal and stimulated cytokine levels using an enzyme-linked immunosorbent assay (ELISA). Results. We revealed a significant reduction in TNF-α secretion in CRC monocytes after initial LPS stimu-lation, with no subsequent recovery upon restimulation. In contrast, IL-1β secretion elevated markedly in CRC patients, particularly after restimulation. These results suggest an impaired TNF-α response and an exacerbated IL-1β response in CRC, indicating a potential immune tolerance mechanism that may contribute to tumor progression. The distinct cytokine dynamics observed point at complex immune dysregulation within the CRC microenvironment. Conclusion. The observed cytokine secretion patterns may indicate immune dysregulation in the microen-vironment of CRC. Our study underscores the importance of understanding the specific roles of cytokines in CRC pathogenesis and highlights the potential for targeted therapeutic interventions to modulate these immune responses. Further research is necessary to explore the underlying signaling pathways and the broader implications of these findings for CRC treatment strategies. This work provides critical insights into the pro-inflammatory cytokine profiles in CRC, advancing our understanding of the immune landscape in cancer and opening new avenues for therapeutic exploration. © Shakhpazyan N.K., Mikhaleva L.M., Sadykhov N.K., Bedzhanyan A.L., Gioeva Z.V., Mikhalev A.I., Pechnikova V.V., Midiber K.Yu., Orekhov A.N., 2024.