TY - JOUR
T1 - Prognostic Implications of the Immune Tumor Microenvironment in Patients with Pancreatic and Gastrointestinal Neuroendocrine Tumors
AU - Baretti, Marina
AU - Zhu, Qingfeng
AU - Zahurak, Marianna
AU - Bhaijee, Feriyl
AU - Xu, Haiying
AU - Engle, Elizabeth L.
AU - Kotte, Anil
AU - Pawlik, Timothy M.
AU - Anders, Robert A.
AU - De Jesus-Acosta, Ana
N1 - Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Objectives The aim of this study was to characterize the tumor microenvironment of patients with gastroenteropancreatic neuroendocrine tumors relative to progression-free survival (PFS). Methods Immune profiling for CD3, CD8, programmed death-1/programmed death-ligand 1, and indoleamine 2,3-dioxygenase expression in 2 cohorts of gastroenteropancreatic neuroendocrine tumors: patients with short PFS (<4 years, n = 12) versus long PFS (≥4 years, n = 14) after surgery. Immune infiltrates in the tumor and interface were quantified. Programmed death-ligand 1 expression was determined within the tumor, stroma, and interface. Results Patients with shorter PFS had larger tumors (P = 0.02), mostly in the pancreas (P = 0.04). We observed a higher mean expression of CD3+, CD8+, programmed death-1+ cells, and indoleamine 2,3-dioxygenase at the interface compared with the tumor: log 10 mean differences 0.56 (95% confidence interval [CI], 0.43-0.68; P < 0.0001), 0.45 (95% CI, 0.32-0.59; P = 0.0002), 0.50 (95% CI, 0.40-0.61; P < 0.0001), and 0.24 (95% CI, 0.03-0.46; P = 0.046), respectively. Patients with longer PFS had higher intratumoral CD3+ T cells, log 10 mean difference 0.38 (95% CI, 0.19-0.57; P = 0.004). Programmed death-ligand 1 expression tended to be higher among patients with shortened PFS (odds ratio, 2.00; 95% CI, 0.68-5.91). Conclusions Higher intratumoral CD3+ T-cell infiltrate was associated with longer PFS after resection.
AB - Objectives The aim of this study was to characterize the tumor microenvironment of patients with gastroenteropancreatic neuroendocrine tumors relative to progression-free survival (PFS). Methods Immune profiling for CD3, CD8, programmed death-1/programmed death-ligand 1, and indoleamine 2,3-dioxygenase expression in 2 cohorts of gastroenteropancreatic neuroendocrine tumors: patients with short PFS (<4 years, n = 12) versus long PFS (≥4 years, n = 14) after surgery. Immune infiltrates in the tumor and interface were quantified. Programmed death-ligand 1 expression was determined within the tumor, stroma, and interface. Results Patients with shorter PFS had larger tumors (P = 0.02), mostly in the pancreas (P = 0.04). We observed a higher mean expression of CD3+, CD8+, programmed death-1+ cells, and indoleamine 2,3-dioxygenase at the interface compared with the tumor: log 10 mean differences 0.56 (95% confidence interval [CI], 0.43-0.68; P < 0.0001), 0.45 (95% CI, 0.32-0.59; P = 0.0002), 0.50 (95% CI, 0.40-0.61; P < 0.0001), and 0.24 (95% CI, 0.03-0.46; P = 0.046), respectively. Patients with longer PFS had higher intratumoral CD3+ T cells, log 10 mean difference 0.38 (95% CI, 0.19-0.57; P = 0.004). Programmed death-ligand 1 expression tended to be higher among patients with shortened PFS (odds ratio, 2.00; 95% CI, 0.68-5.91). Conclusions Higher intratumoral CD3+ T-cell infiltrate was associated with longer PFS after resection.
KW - GEP-NETs
KW - PD-1
KW - PD-L1
KW - prognosis
KW - spatial architecture
KW - tumor-infiltrating lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=85108021207&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85108021207&partnerID=8YFLogxK
U2 - 10.1097/MPA.0000000000001831
DO - 10.1097/MPA.0000000000001831
M3 - Article
C2 - 34016898
AN - SCOPUS:85108021207
SN - 0885-3177
VL - 50
SP - 719
EP - 726
JO - Pancreas
JF - Pancreas
IS - 5
ER -