Tumor serotonin drives macrophage-mediated resistance to tarlatamab in lung neuroendocrine cancer

A study by Nomura et al., published in Cancer Cell, shows that lung neuroendocrine cancers produce serotonin that acts through the HTR7 pathway to shape immunosuppressive macrophages. These macrophages mediate resistance to the T cell engager tarlatamab and to immune checkpoint blockade. The mechanism was demonstrated in both small cell lung cancer and large cell neuroendocrine carcinoma, the two main lung neuroendocrine cancer types. The work identifies tumor-derived serotonin signaling as a neuroimmune route of treatment resistance and points to HTR7 as a potentially druggable therapeutic vulnerability, suggesting that blocking this pathway could restore sensitivity to tarlatamab and immunotherapy. Follow-up work on HTR7-targeting strategies and clinical translation is still open.

Written by a model from the reports · updated 4 hours ago