ECE2022 Poster Presentations Endocrine-Related Cancer (41 abstracts)
Uncovering the immune profile in well-differentiated gastroenteropancreatic neuroendocrine tumors
Franz Sesti 1 , Giulia Puliani 1,2 , Francesca Sciarra 1 , Tiziana Feola 1,3 , Roberta Centello 1 , Valentina Di Vito 1 , Carla Pandozzi 1 , Andrea Lenzi 1 , Andrea Isidori 1 , Mary Anna Venneri 1 , Antongiulio Faggiano 4 & Elisa Giannetta 1
1Sapienza University of Rome, Department of Experimental Medicine, Roma, Italy; 2IRCCS Regina Elena National Cancer Institute, Oncological Endocrinology Unit, Roma, Italy; 3IRCCS Neuromed Mediterranean Neurological Institute, Neuroendocrinology, Pozzilli, Italy; 4Sapienza University of Rome, Department of Clinical and Molecular Medicine, Italy
Introduction: Immune tumor microenvironment plays a key role in tumors’ growth and metastatic spread, while its role in the heterogeneous field of neuroendocrine neoplasms (NENs) remains unclear. There is evidence that tumor progression in NENs is promoted by an immunosuppressed microenvironment created by a plethora of infiltrating immune cells. Changes in circulating leukocyte and peripheral blood mononuclear cell (PBMC) subpopulations can mirror the local alteration of the microenvironment, as demonstrated in different kinds of tumors but data in NENs are lacking.
Methods: A prospective controlled observational study was performed recruiting 15 consecutive patients naïve to treatment with histologically proven gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and 15 healthy controls (Ctrl), matched for age and sex. The primary aim was the quantification of PBMC subpopulations (profiled via flow cytometry).
Results: The mean age of the patients was 60.3±9.7 years (73.3% males). G1 NETs were 46.7%, G2 were 53.3%. Locally advanced or metastatic disease represented the 80%. Immune cell profiling revealed a lower CD3-CD56+ natural killer (NK) cell count in patients with NET than in Ctrl (median [interquartile range], 124 [90-572 vs 402 [265-530] cells/μl; p=0.04). NK subset analysis showed a reduced percentage of CD56+CD16+ NK cells (81.8% [76.8-89.7%] vs 91.7 [88.9-97.6%]; p=0.004), a reduced absolute count of CD56+CD16+ NK cells (114 [73-468] vs 340 [247-480] cells/μl; p=0.026), and a reduced absolute count of CD56dim NK cells (105 [66-544] vs 362 [237-461] cells/μl; p=0.04) in patients than in Ctrl. Total monocytes count was not significantly different between the study groups. However, patients with NET had a higher percentage of CD14+CD16++ non-classical monocytes (3.3% [2.1-9.1%] vs 1.7% [1.1-2.5%]; p=0.01), a higher absolute count of CD14+CD16++ non-classical monocytes (14 [6-23] vs 6 [3-10] cells/μl;P=0.019), and a lower percentage of CD14+CD16+ intermediate monocytes (5% [2.6-9.2%] vs 8.8% [6.1-11.6%]; p=0.04). Total CD3+ T lymphocyte count was not significantly different between the study groups. However, a decrease in percentage (mean ± standard deviation, 55.4±8.1% vs 63.9±6.6%; p=0.004) and in absolute count (554±307 cells/μl vs 820±285 cells/μl; p=0.02) of CD4+ T helper lymphocytes were found in NETs patients.
Conclusions: The study shows that patients with GEP-NETs have an immune alteration characterized by a low count of cytotoxic NK cells and a high count of anti-inflammatory non-classical monocytes, suggesting a deregulation of CD16 expressing cells. Moreover, a low count of T helper lymphocytes was found. This unfavorable and immunosuppressed immune profile could contribute to tumor growth and progression.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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