PhD Scientific Days 2022

Pathology and Oncology III. (Poster discussion will take place in the Aula during the Coffee Break)

The Immunological Landscape of Surgically Resected Pulmonary Neuroendocrine Tumors

Text of the abstract

Introduction: Although immunotherapy has led to a paradigm shift in the treatment of lung cancer, the clinical progress concerning the diagnostic and therapeutic approaches in pulmonary neuroendocrine lung tumors (i.e. atypical carcinoids [AC], large cell neuroendocrine lung cancer [LCNEC], small cell lung cancer [SCLC]) still lags behind that seen in non-small cell lung cancer.
Aims: Our aim was to investigate the expression profile of immunological markers in the tumor microenvironment of surgically resected pulmonary neuroendocrine carcinomas.
Methods: Formalin-fixed paraffin-embedded tumor samples from 26 AC, 30 LCNEC and 29 SCLC patients who underwent lung resection surgery were retrospectively collected from two Hungarian institutions. Expression pattern of 10 immunological markers (PD-1, CD27, CD4, ICOS, CD40, CD47, LAG-3, NKG2A, OX40 and IDO) of tumors cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters.
Results: In general, AC samples showed the lowest immune response rate concerning the expression profile of the examined markers, whereas LCNEC and SCLC samples tended to have considerably stronger immune responses. Notably, CD47 expression of TILs was also significantly higher in LCNEC and SCLC samples than in AC specimens (p=0,017 and p=0,0079, respectively). Likewise, TIL PD-1 expression was as well considerably higher in LNCEC and SCLC tumors compared to AC cases (p<0.001). As for the TCs, we found that ACs have higher CD40 and NKG2A expression levels compared to the high-grade tumors. Unsupervised hierarchical clustering of TC expression of the aforementioned markers separates the specimens according to their histological subtype.
Conclusion: Our results show that AC tumors have a bleak immunological landscape, whereas the majority of highly aggressive LCNEC and SCLC samples are dominated by high expression of immunological markers. By providing insights into the immunological landscape of pulmonary neuroendocrine tumors, our results might contribute to the development of novel immunotherapy-related therapeutic approaches in these highly aggressive malignancies.
Funding: Bence Ferencz is a recipient of the Semmelweis 250+ Excellence PHD scholarship of the Semmelweis University.