Lung cancer accounts for 12% of all new cases of cancers worldwide with small cell lung carcinoma (SCLC) representing 13% of the newly diagnosed lung cancers. Treatment of SCLC remains challenging because of its rapid growth, early dissemination and development of drug resistance during the course of the disease. Many current studies aim at developing more specific ways of treating this cancer. These include, immunotherapy, which utilizes the unique specificity of the immune system in order to attack the transformed cells, while leaving the normal cells unharmed.
Our research focuses on discovery of peptides presented by the HLA complexes of SCLC cells, while looking for peptides - with potential to serve as targets for immunotherapy. Since the expression of class I HLA molecules on SCLC cells is lower than on normal lung cells, our goal is also to find new treatments, including cytokines (such as interferon gamma) and other chemotherapy agents, to increase the expression of HLA molecules on the cells’ surface and facilitate recovery of specific peptides.
By using tandem mass-spectrometer analysis we identified more than 3500 different HLA class I peptide, from different purifications of untreated and treated with interferon gamma (IFNγ) NCI-H82, NCI-H526 and NCI-H69 cell lines. We observed a significant increase in the number of purified HLA class I molecules after the treatment, and confirm the increase in expression also by Western blot, flow cytometry and confocal microscopy analyses.
A small percentage of the identified HLA peptides were derived from putative tumor associated antigens. These genes are known to be expressed especially in cancer cells or in immune privileged tissues. Such peptides and their source proteins are potentially advantageous as candidates for cancer vaccines or tumor markers.
