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- Title
Expression and Prognostic Value of B7 Family Immune Checkpoints in Pancreatic Neuroendocrine Tumors.
- Authors
Shengwei Mo; Liju Zong; Xianlong Chen; Xinchao Ban; Mei Li; Zhaohui Lu; Shuangni Yu; Jie Chen
- Abstract
* Context.--Pancreatic neuroendocrine tumors (PanNETs) are rare malignancies with heterogeneous clinical courses requiring novel prognosticators and therapies. B7 family molecules have an important role in various cancers; however, these have not been distinguished in PanNETs. Objective.--To investigate the expression and clinical significance of programmed death ligand-1 (PD-L1), programmed death ligand-2 (PD-L2), B7 homolog 3 (B7- H3), B7 homolog 4 (B7-H4), and V-domain immunoglobulin suppressor of T-cell activation (VISTA) in 182 PanNETs (with a high proportion of functioning versus nonfunctioning PanNETs: 51% versus 49%). Design.--Molecules were immunostained by using tissue microarrays from 182 patients with grade 1/2 PanNETs. VISTA-positive microvessel density (VISTA+ MVD) was evaluated in 4 high-power fields (HPFs) (x 200) and mean count was calculated; immune cells with 1% or greater VISTA staining were considered positive. PD-L1 tumoral expression was considered positive in samples with 5% or more membranous staining. Tumoral VISTA, stromal PD-L1, PD-L2, B7-H3, and B7-H4 expression were deemed positive if any staining was observed. Results.--VISTA+ MVD was high (≥10.8/HPF) in 45 patients (25%), while VISTA stained positively on immune and tumor cells in 121 (66%) and 0 patients, respectively. Positive PD-L1 tumoral and stromal expression was observed in 23 (13%) and 0 patients, with positive B7- H3 expression in 76 (42%) and 98 (54%) patients, respectively, in these cells; PD-L2 and B7-H4 were not detected. PD-L1 positivity rate was high in functioning PanNETs. Stromal B7-H3 and high VISTA+ MVD correlated with unfavorable clinicopathologic features. Moreover, high VISTAþ MVD was an independent predictor of shorter progression-free survival. Conclusions.--VISTA may serve as a prognosticator and immunotherapeutic target for patients with pancreatic neuroendocrine tumor (PanNET).
- Subjects
PANCREATIC tumors; IMMUNE checkpoint inhibitors; PROGRAMMED death-ligand 1; STAINS &; staining (Microscopy); ISLET cell tumor; REGULATORY T cells; GENE expression; NEUROENDOCRINE tumors; DESCRIPTIVE statistics; PROGRESSION-free survival; DATA analysis software; IMMUNOTHERAPY; ANTIGENS
- Publication
Archives of Pathology & Laboratory Medicine, 2023, Vol 147, Issue 2, p193
- ISSN
0003-9985
- Publication type
Article
- DOI
10.5858/arpa.2021-0377-OA