The immunologic landscape of intermediate- and high-grade neuroendocrine lung tumors
Ferencz Bence
KÁROLY RÁCZ CONSERVATIVE MEDICINE PROGRAM
Dr. Reusz György
Országos Korányi Pulmonológiai Intézet, J épület
2024-11-26 15:15:00
Pulmonology
Dr. Losonczy György
Dr. Megyesfalvi Zsolt
Dr. Forika Gertrúd
Dr. Csoma Zsuzsanna
Dr. Nagy Péter
Dr. Rácz Gergely
Dr. Tóth Erika
Intermediate-, and especially high-grade neuroendocrine lung neoplasms are aggressive tumors, with high metastatic potential and poor prognosis. Due to their relative rarity and complex biology, our knowledge of these entities remains very limited. In the last few years, molecular studies have shed more light on these tumors, thus bringing us closer to understand their development and behavior. However, there are still many gaps in our knowledge regarding their treatment; consequently, the therapeutic arsenal has not changed significantly over the past 30 years. Therefore, it is of utmost importance to understand the microenvironment of LNENs, map their TIM, and thereby identify potential therapeutic targets for future investigations. To answer these questions, we examined surgically resected histological samples from a total of 156 patients diagnosed with LNENs (26 AC, 64 LCNEC and 66 SCLC). A total of 19 immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD27, CD47, IDO, ICOS, CD70, CD137, CD40, NKG2A, LAG3, OX40, VISTA, OX40L, GITR and TIM3) were used to explore the tumor immune profile.
Our results show a significantly different immune marker expression pattern between these 3 tumor types. Based on this, a well-matched immune marker profile allows a good differentiation between LNENs. The immunological landscape of AC tumors is sparse whereas the majority of highly aggressive LCNEC and SCLC samples are dominated by high expression of immunological markers. In case of the 4 novel immunotherapeutic targets, we have found that ACs have high TIM3 tumor cell expression, GITR is highly expressed in both AC and SCLC tumor cells, while OX40L is most highly expressed in SCLC tumor cells.
Ultimately, since our results provide a deeper understanding of the immunologic nature of these tumors, they represent an important first step towards the development of effective and appropriate immunotherapeutic strategies and immunotherapy-based clinical trials for these deadly diseases.
