Anais Sanchez-Castillo from Maastricht in the Netherlands presented pre-clinical results on the effects of radiotherapy combined with sertraline in non-small cell lung cancer (NSCLC) at the ESTRO 2024 conference. Sertraline, an antidepressant, also inhibits serine/glycine metabolism by targeting the enzyme SHMT2. The study included analysis of patient tumor and blood samples, lung cancer cells cultured in vitro, and a lung tumor immunogenic mouse model.

The results reveal that high expression of enzymes involved in serine/glycine synthesis in lung tumor tissue correlates with poor patient survival. Additionally, high blood plasma levels of serine/glycine metabolites correlate with immune suppression. The enzyme SHMT2 is upregulated in lung cancer models following radiotherapy. Sertraline was found to radiosensitive lung cancer cells both in vitro and in vivo. Moreover, sertraline reduces immune suppression by decreasing the protein expression of the immune checkpoint protein galectin-1 and increasing the expression of granzyme B.

These findings demonstrate that sertraline radiosensitises lung cancer cells and improves tumor control through immunomodulation in NSCLC. Targeting serine/glycine metabolism may be a promising future approach to improve immunotherapy responses in NSCLC.

Randi G. Syljuåsen, PhD

Department of Radiation Biology

Institute for Cancer Research

Oslo University Hospital

Oslo, Norway

Member of the ESTRO Lung Focus Group