Abstract 1234
Background
Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a poorly differentiated grade 3 neuroendocrine neoplasm, of which the overall survival is poor with limited treatment options. Immune checkpoint related therapy such as PD-1 blocking has successfully been used in some solid tumor treatment. In this study, we investigated the infiltration of immune-cells and PD-1/PD-L1 blockade biomarkers to improve understanding of the tumor immune microenvironment in GEP-NEC.
Methods
Stromal and tumor cells expressing CD3, CD8 and CD68 protein were assessed in 32 cases of GEP-NEC by immunohistochemistry. Their tumor mutational burden (TMB) and microsatellite instability (MSI) were measured by gene sequencing. Software mSINGS MSIsensor and MSIseq were used to evaluate MSI and MSI status was set when more than two software showed the MSI. The Mann-Whitney U test and Kruskal-Wallis test were used to analyze the correlation of markers expression with clinicopathological parameters. Kaplan -Meier curves were applied in survival analyses.
Results
In the study, 65.6% of the patients were male and the median age was 65. The predominant primary sites were stomach (66%) and pancreas (19%). High infiltration (more than 25% stromal area infiltration) of CD3, CD8 and CD68 immune cells were found in 84%, 47% and 81% of the patients, respectively. High expression of CD3 correlated with high expression of CD8 and CD68 (p < 0.05). Average of TMB was 5.84 mutations per megabase. 57% of the patients were classified as having intermediate TMB (5-15 mutations/megabase) with the remaining classified as having low TMB (0-5 mutations/megabase). None of the patients was in MSI status under our evaluation. Among the baseline characteristics, patients in stage IV of TNM showed lower CD8 expression (p < 0.05). No significant association was observed between the investigated markers and survival.
Conclusions
The study contributes to the understanding of immune microenvironment of GEP-NEC. The association of clinicopathological features with PD-1/PD-L1 blockade biomarkers and immune cells in GEP-NEC were explored. This understanding should help to improve predictions of the impact of the PD-1/PD-L1 pathway in GEP-NEC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Chinese Academy of Medical Sciences (CAMS) Initiative for innovative Medicine (CAMS-I2M) 2017-I2M-1-001.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3931 - Differences in multikinase inhibitors (MKI) toxicity profile according to gender. A pooled analysis of three phase II trials with lenvatinib, pazopanib and sorafenib in patients (pts) with advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs).
Presenter: Jorge Hernando Cubero
Session: Poster Display session 2
Resources:
Abstract
5458 - Baseline characteristics from CLARINET FORTE: Evaluating lanreotide autogel (LAN) 120 mg every 14 days in patients with progressive pancreatic or midgut neuroendocrine tumours during a standard first-line LAN regimen.
Presenter: Philippe Ruszniewski
Session: Poster Display session 2
Resources:
Abstract
1517 - Diabetes Is Associated With Pancreatic Neuroendocrine Tumors Growth and Metastasis
Presenter: Zhiyao Fan
Session: Poster Display session 2
Resources:
Abstract
2145 - Investigation of the reclassification of G1/G2 pancreatic neuroendocrine neoplasms by WHO 2017 classification
Presenter: Takahiro Yokose
Session: Poster Display session 2
Resources:
Abstract
3134 - Treatment with somatostatin analogues after radiopeptide therapy
Presenter: Daria Handkiewicz Junak
Session: Poster Display session 2
Resources:
Abstract
2191 - Safety and Tolerability of Surufatinib in Western Patients with Solid Tumors
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3253 - The impact of tumour absorbed dosimetry with survival outcomes after peptide receptor radionuclide therapy in metastatic neuroendocrine tumours.
Presenter: Rahul Ladwa
Session: Poster Display session 2
Resources:
Abstract
3581 - Opportunist and Serious Infections in Patients with Neuroendocrine Tumors Treated With Everolimus: A Multicenter Study of Real World Patients
Presenter: Carine Mauro
Session: Poster Display session 2
Resources:
Abstract
5374 - Establishment of Prognostic Nomogram Based on the Metastatic Lymph Nodes Ratio for Patients with Gastric Neuroendocrine Tumour
Presenter: yaobin lin
Session: Poster Display session 2
Resources:
Abstract
3951 - Neutrophil-lymphocyte ratio as an independent predictive factor in Neuroendocrine Neoplasms
Presenter: Sofia Ferreira
Session: Poster Display session 2
Resources:
Abstract