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
870 - Selective Wnt/β-catenin small-molecule inhibitor CWP232228 impairs tumor growth of colon cancer
Presenter: Jin Young Kim
Session: Poster Display session 2
Resources:
Abstract
3425 - Feasibility and impact of prospective DPYD screening in the Irish population
Presenter: Mohammed Zameer
Session: Poster Display session 2
Resources:
Abstract
1972 - Diet-derived metabolites and the risk of colorectal cancer: a nested case-control study in a population-based cohort, the Singapore Chinese Health Study
Presenter: Dawn Chong
Session: Poster Display session 2
Resources:
Abstract
4103 - Loss of subcutaneous adipose tissue during chemotherapy predicts reduced survival in patients with incurable colorectal cancer undergoing palliative therapy
Presenter: Erin Stella Sullivan
Session: Poster Display session 2
Resources:
Abstract
4309 - Obese and overweight is associated with better prognosis in metastatic colorectal cancer patients treated with bevacizumab.
Presenter: Bozena Cybulska-Stopa
Session: Poster Display session 2
Resources:
Abstract
3554 - Patient characteristics associated with poor performance status, ECOG 2-3, and effect on survival in 1086 Finnish metastatic colorectal cancers (mCRC) nationwide (prospective RAXO study)
Presenter: Pia Österlund
Session: Poster Display session 2
Resources:
Abstract
4572 - Discovery and Diagnosis of Metastatic Colorectal Cancer (mCRC) in the Real World: Final Results from a European Survey
Presenter: Iga Rawicka
Session: Poster Display session 2
Resources:
Abstract
4783 - Adherence to recommended intake of calcium and colorectal cancer risk in the HEXA study
Presenter: Jeeyoo Lee
Session: Poster Display session 2
Resources:
Abstract
5106 - Body size, sex and sidedness of incident colorectal cancer in a prospective Swedish cohort study
Presenter: Christina Siesing
Session: Poster Display session 2
Resources:
Abstract
3364 - Middle East & North Africa Registry to characterize RAS mutation status and tumor specifications in recently diagnosed patients with metastatic colorectal cancer (MORE-RAS Study)
Presenter: Mohamed Oukkal
Session: Poster Display session 2
Resources:
Abstract