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John Gordon: SERT as a Novel Target in Cancer Immunotherapy via SSRIs

John Gordon/LinkedIn

May 23, 2025, 11:16

John Gordon: SERT as a Novel Target in Cancer Immunotherapy via SSRIs

John Gordon, Co-Founder, Director and VP of Scientific Affairs at Celentyx, shared a post on LinkedIn:

“Antidepressants: A “Dead SERT” for Tumor Therapy. Breaking OPEN ACCESS Study from Lili Yang & Friends at Cell Press. Synergy between Prozac & Immune Checkpoint Inhibition against Solid Cancers.

Identifying additional immune checkpoints hindering antitumor T cell responses is key to the development of next-generation cancer immunotherapies. Here, researchers report the induction of serotonin transporter (SERT), a regulator of serotonin levels and physiological functions in the brain and peripheral tissues, in tumor-infiltrating CD8 T cells.

Inhibition of SERT using selective serotonin reuptake inhibitors (SSRIs), the most widely prescribed antidepressants, significantly suppressed tumor growth and enhanced T cell antitumor immunity in various mouse syngeneic and human xenograft tumor models.

Importantly, SSRI treatment exhibited significant therapeutic synergy with programmed cell death protein 1 (PD-1) blockade, and clinical data correlation studies negatively associated intratumoral SERT expression with patient survival in a range of cancers. Mechanistically, SERT functions as a negative-feedback regulator inhibiting CD8 T cell reactivities by depleting intratumoral T cell-autocrine serotonin.

These findings highlight the significance of the intratumoral serotonin axis and identify SERT as an immune checkpoint, positioning SSRIs as promising candidates for cancer immunotherapy.

See also:
1. Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells.

2. The serotonin transporter is present in B-cell clones of diverse malignant origin: a potential anti-tumor target for psychotropics.

3. SLC6A4 expression & anti-proliferative responses to serotonin transporter ligands in primary B-cell malignancies.”

More posts featuring John Gordon.

Antidepressants cancer CD8+ T cells Celentyx Cell Press fight against cancer Global fight against cancer immune checkpoint inhibition immunotherapy John Gordon Lili Yang OncoDaily Oncology serotonin transporter SERT SSRIs Tumor Therapy

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