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
5185 - Systemic administration of the hyaluronidase-expressing oncolytic adenovirus VCN-01 in patients with advanced or metastatic pancreatic cancer: first-in-human clinical trial
Presenter: Rocio Garcia-Carbonero
Session: Poster Display session 2
Resources:
Abstract
4842 - The analysis of genomic signatures of head and body/tail of pancreatic cancer in Chinese patients
Presenter: Qi Ling
Session: Poster Display session 2
Resources:
Abstract
4988 - MGMT methylation in metastatic pancreatic cancer (mPAC): a single center experience
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5035 - Advantage of three-dimensional image analysis of pancreatic cancer using computed tomography
Presenter: Seung Bae Yoon
Session: Poster Display session 2
Resources:
Abstract
1465 - Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) with S-1 in patients with stage IV pancreatic cancer.
Presenter: Susumu Hijioka
Session: Poster Display session 2
Resources:
Abstract
1982 - Impact of anatomic site of biliary tract tumour origin and conditional probability of survival (CS): results from 15 prospective advanced first-line clinical trial
Presenter: Mairead McNamara
Session: Poster Display session 2
Resources:
Abstract
2244 - FOLFOXIRI versus FOLFIRINOX in first-line chemotherapy in patients with advanced pancreatic cancer: a propensity score analysis
Presenter: Angélique Vienot
Session: Poster Display session 2
Resources:
Abstract
4557 - Cellfree tumor-DNA (cfDNA) as a very early predictor of therapeutic outcome in pancreatic ductal adenocarcinoma (PDAC)
Presenter: Sabine Payr
Session: Poster Display session 2
Resources:
Abstract
4406 - Comprehensive genomic profiling (CGP) of gall bladder adenocarcinoma (GBAC) in patients from distinct ancestral populations
Presenter: Milind Javle
Session: Poster Display session 2
Resources:
Abstract
4283 - Phase II Monotherapy Efficacy of Cancer Metabolism Targeting SM-88 in Heavily Pre-Treated PDAC Patients.
Presenter: Allyson Ocean
Session: Poster Display session 2
Resources:
Abstract