Project leaders: Ágnes Paál, Anikó Görbe


Small cell lung cancer (SCLC) is one of the malignancies with the worst prognosis, for which there have been no significant advances in therapy over the last three decades. The first promising results have been with the use of immune checkpoint inhibitors (ICIs), but success is far below that seen in non-small cell lung cancer, where the use of ICIs has been a breakthrough in therapy. In SCLC, in some patients with extensive-stage disease, survival can be 1-2 months longer.


Microscopoical image of small round cells in small cell lung cancer
SCLC cells in culture


These suggest that new approaches are needed to understand response and resistance of SCLC to Immunotherapy. Several research groups have identified molecular subtypes of SCLC, which partially correspond to each other. For example, weaker neuroendocrine marker expression is often associated with stronger immune infiltration (neuroendocrine-low, immune oasis tumors), which may suggest better Immunotherapy responsiveness in such tumors.


A possible road to improved therapy: evolving subclassifciation of SCLC


Despite stronger immune infiltration, tumors do not always respond to ICIs, and local overexpression of immunosuppressive molecules has been detected.

We investigate the effects of silencing gene expression of one of these immunosuppressive molecules, annexin A1, in cell culture of neuroendocrine-low SCLC cell lines. We hypothesize that some features of the malignant phenotype may be affected by annexin A1 silencing, such as growth rate, epithelio-mesenchymal transition, metabolic shift, dominant transcription drivers and sensitivity to the classical chemotherapeutic agents, cisplatin and etoposide.


Fluorescent viability assay


We believe that studying the effects of annexin A1 silencing may help understand new aspects of small cell lung cancer that are relevant in therapy.


Learning opportunities:

– culturing of small cell lung cancer cell lines

– assessment of growth rate by cell counting and fluorescence viability assays

– treatment of cells and chemosensitivity tests with fluorescence viability assays

– western blot




Related publications:

  • Dora, David et al. “Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution.” Molecular oncology 14,9 (2020): 1947-1965. doi:10.1002/1878-0261.12741
  • Dora, David et al. “Characterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer.” Biology 10,6 502. 4 Jun. 2021, doi:10.3390/biology10060502
  • Dora, David et al. “Protein Expression of immune checkpoints STING and MHCII in small cell lung cancer.” Cancer immunology, Immunotherapy : CII vol. 72,3 (2023): 561-578. doi:10.1007/s00262-022-03270-w