Profiling of DNA damage and repair pathways in small cell lung cancer reveals a suppressive role in the immune landscape

Target gene sequencing reveals that DNA damage response (DDR) pathway alterations in SCLC, both double strand breaks (DSB) and single strand breaks (SSB), have a positive correlation with high tumor mutation burden (TMB) [3]. [...]we found that the process of homologous DNA pairing and Strand Exchange in homologous recombination (HR) of doubles strand breaks (DSB) repair negatively correlates with the overall immune landscape in SCLC patients. The results showed that homologous DNA pairing and strand exchange pathway (labeled as G4) negatively correlated with the immune content (Fig. 1F). Since RAD51 is the critical player in DNA pairing and strand exchange process of HR, we further investigated if RAD51 inhibition could affect the immune checkpoint molecules expressions after DNA damage. Genetic variation in glutathione metabolism and DNA repair genes predicts survival of small-cell lung cancer patients.