Endocrine Abstracts

Background: Lanreotide is clinically effective in advanced neuroendocrine tumors (NETs). The inhibitory effect of lanreotide on tumor cells proliferation is due to binding to somatostatin receptors (SSTR1-5). It has been demonstrated that immune cells express SSTR1-5 differentially. The exact effect of somatostatin analogs (SSAs) on T cell function is not understood.

Methods: In vitro and in vivo effects of lanreotide on immune cells were investigated, with clinical response correlates. In vitro, SSTR1-5 expression was measured on CD4+ T helper cells, CD8+ cytotoxic T cells, and CD4+CD25+ T regulatory cells from healthy donors (HD), and lanreotide effect on key functional immune response parameters were studied. To assess in vivo effects of lanreotide on immune cells of NET pts, peripheral blood mononuclear cells (n=17) obtained pre and 3 months post treatment were studied for gene and protein expression profiles in sorted T cell subsets using NanoString immune cell panel.

Results: HD T cells had high expression of SSTR2 and low/no expression of other SSTRs. In vitro, lanreotide had no effect on functional immune response parameters investigated. For the in vivo study, the patient cohort consisted of 9 responders and 8 non-responders. Clinicopathological features, see table. Pretreatment immunological competence of responders was greater than non-responders, indicated by upregulation of TCR signaling (in CD4+) and interferon signaling (in CD8+ and T reg). Irrespective of clinical response, lanreotide had most significant effect on CD8+ T cells, downregulating WNT, TCR, and NF-kB signaling. Compared to non-responders, responders had downregulation of cytokine and chemokine signaling but upregulation of ubiquitination and proteasome degradation associated genes. Several myeloid specific genes were significantly changed in the CD4 T helper population, possibly due to co-isolated myeloid cells interacting with T cells during sorting.

Conclusion: The in vivo immune effects of lanreotide seen in the absence of in vitro effects reflect the relevance of environmental parameters such as interactions with myeloid components of the immune system not accounted for under the experimental in vitro conditions.

Abstract ID 21431