Assessment of inflammatory marker expression and immune phenotypes in lung cancer
Török Klára
KÁROLY RÁCZ CONSERVATIVE MEDICINE PROGRAM
Dr. Fekete Andrea
Országos Onkológiai Intézet, Előadóterem 3. épület fsz.
2025-10-21 13:00:00
Pulmonology
Dr. Losonczy György
Dr. Megyesfalvi Zsolt
Dr. Piros László
Dr. Buzás András
Dr. Zima Endre
Dr. Huszty Gergely Dénes
Dr. Dede Kristóf
Dr. Sótonyi Péter
Our work emphasizes the complexity of LADC and LNENs. It highlights the importance of histological diversity, genetic variability, inflammation, and the dynamics of the immune microenvironment. The initial study focused on the heterogeneity of LADC, examining the KRAS mutation status, its relationship with histopathological growth patterns, and the role of NLRP3 inflammasome activation in the immune response.
In our analysis, 19 cases exhibited significant intratumoral heterogeneity in KRAS mutations, indicating genetic variability within the tumor. According to the growth pattern, it can be said that KRAS G12C mutations were present in lepidic LADC, while wild-type KRAS gene mutations were absent in micropapillary LADC. Nevertheless, we did not find a significant correlation between KRAS mutations, histological growth patterns, and mucin secretion. Beyond histological and genetic analysis, we explored the expression of the inflammatory factor NLRP3 and its relationship with immune cell infiltration and the TIM. Our findings indicate that high NLRP3 expression is associated with an inflammatory microenvironment and increased immune cell infiltration, yet no significant correlation was observed between NLRP3 expression and KRAS mutational status.
In the second part of our research, we analyzed the expression of four immunotherapeutic markers (VISTA, OX40L, GITR, TIM3) in LNENs to gain deeper insights into the tumor immune microenvironment and potential therapeutic targets. Our findings reveal distinct patterns of immune checkpoint expression across LNEN subtypes, with ACs exhibiting high TIM3 expression in tumor cells. In contrast, we observed an increase in GITR expression in ACs and SCLCs. In the case of OX40L, the highest values were observed in SCLCs. In ACs, as intermediate-grade malignant tumors, the expression levels of OX40L, VISTA, and GITR were also significantly lower. All these results may indicate significant differences in immune regulation between specific subtypes. These extensive results contribute to a better understanding of immune modulation in pulmonary malignancies and provide a foundation for future targeted immunotherapeutic strategies.
