Pathway from Scientific Research

Schematics showing the intratumoral serotonin axis in analogy to the serotonin axis in the neuron. In an antitumor CD8 T cell, TPH1 converts Trp into 5-HT, which is secreted into the tumor microenvironment (TME) and in turn stimulates the T cell by binding to its surface 5-HTR. SERT depletes 5-HT from the TME by transporting it back into the T cell, where it is degraded by MAO-A into 5-HIAL. SSRIs can inhibit SERT activity, increasing extracellular 5-HT and preventing degradation. TPH1/2, tryptophan hydroxylase 1/2; Trp, tryptophan; 5-HT, 5-hydroxytryptamine or serotonin; 5-HTR, 5-HT receptor; SERT, serotonin transporter; MAO-A, monoamine oxidase A; 5-HIAL, 5-hydroxyindolealdehyde; SSRIs, selective serotonin reuptake inhibitors; TCR, T cell receptor; MHC, major histocompatibility complex; DC, dendritic cell; TAM, tumor-associated macrophage.

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