Abstract
Octreotide long-acting repeatable (LAR) is largely used to treat functional and/or metastatic neuroendocrine neoplasms (NENs). Its effect in controlling carcinoid syndrome and partially reduce tumour burden is attributable to the ability of octreotide to bind somatostatin receptors (SSTRs) on the tumour and metastasis, regulating growth hormone secretion and cell growth. Notably, SSTRs are also expressed, at different levels, on Tregs. Tregs, together with myeloid-derived suppressor cells (MDSCs), are key components in the anti-tumour immunoregulation. This is the first prospective study aimed to explore the impact of Octreotide (OCT) LAR on the immune system, with a particular focus on Tregs and MDSC cells. Here, we show that circulating Tregs are elevated in NENs patients compared to healthy donors and that treatment with OCT LAR significantly decrease the level of total Tregs and of the three functional Tregs populations: nTregs, eTregs and non-Tregs. Furthermore, OCT LAR treatment induces a functional impairment of the remaining circulating Tregs, significantly decreasing the expression of PD1, CTLA4 and ENTPD1. A trend in circulating MDSC cells is reported in patients treated with OCT LAR. The results reported here suggest that the effect of OCT LAR on Tregs could tip the balance of the patients’ immune-system towards a durable anti-tumour immunosurveillance with consequent long-term control of the NENs disease.
Highlights
Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies derived from the neuroendocrine cell compartment [1]
Peripheral Tregs were evaluated at T0 in 35 neuroendocrine neoplasms (NENs) patients and 23 healthy donors (HD)
We showed a significant reduction in Tregs and Tregs subpopulation, eTregs, naïve Tregs (nTregs) and non-Tregs, in metastatic GEP-neuroendocrine tumours (NETs) and lung-NETpatients during treatment with OCT long-acting repeatable (LAR)
Summary
Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies derived from the neuroendocrine cell compartment [1]. NENs incidence and prevalence are steadily increasing due to the improvement of diagnostic and therapeutic tools; the large part of patients presents with advanced and symptomatic disease [2]. While chemotherapy (platinum-based) is the mainstay of treatment for neuroendocrine carcinomas (NECs), somatostatin analogs (SSAs: octreotide and lanreotide) represent the backbone of the treatment for well-differentiated neuroendocrine tumours (NETs). SSAs play a key role in controlling hormone-related symptoms (carcinoid syndrome) and improving clinical benefit [3,4,5]. SSAs mainly act inhibiting tumour growth; this results in a good disease control but in a weak tumour shrinkage effect. Octreotide (OCT) long-acting release (LAR) showed an objective response rate (ORR) of 3–10%, but the disease stabilization rates were up to
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