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
2667 - The impact of late-line treatment on overall survival (OS) from the initiation of first-line chemotherapy (CT) for patients (pts) with metastatic colorectal cancer (mCRC).
Presenter: Takeshi Kawakami
Session: Poster Display session 2
Resources:
Abstract
3139 - Efficacy and safety of FOLFIRI/Aflibercept (FA) in elderly population with mCRC after failure of oxaliplatin-based chemotherapy.
Presenter: Nieves Martinez Lago
Session: Poster Display session 2
Resources:
Abstract
3446 - Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: preliminary data from the prospective observational CHECKPOINT trial (NCT02665312)
Presenter: Pasquale Lombardi
Session: Poster Display session 2
Resources:
Abstract
3969 - Comparable survival outcome between Thai patients with sporadic young adult and adult onset colorectal cancer
Presenter: Kanjana Sukhokanjanachusak
Session: Poster Display session 2
Resources:
Abstract
4455 - Impact of primary tumor side on 3-year survival outcomes of first-line (1L) FOLFOX-4 ± cetuximab in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the phase 3 TAILOR trial
Presenter: Shukui Qin
Session: Poster Display session 2
Resources:
Abstract
4481 - Undetectable RAS mutant clones in plasma: possible implication for therapy and prognosis in the patient with RAS mutant metastatic colorectal cancer?
Presenter: Mohamed Bouchahda
Session: Poster Display session 2
Resources:
Abstract
5074 - Dihydropyrimidine dehydrogenase (DPD) determination prior the administration of medicines containing fluorouracil: a single Spanish hospital experience.
Presenter: Maria Dolores Mediano Rambla
Session: Poster Display session 2
Resources:
Abstract
5242 - Differences in survival between right and left-sided colorrectal cancer (CRC) in every stage, a CARESS-CCR Group Study.
Presenter: Julia Alcaide-Garcia
Session: Poster Display session 2
Resources:
Abstract
1123 - Quality of Life (QoL) in patients with aflibercept (AFL) and FOLFIRI for metastatic colorectal cancer (mCRC) – Interim analysis with focus on mutational status of the non-interventional study QoLiTrap (AIO-LQ-0113)
Presenter: Roger von Moos
Session: Poster Display session 2
Resources:
Abstract
1212 - The cost of adverse event management in patients with RAS wild-type metastatic colorectal cancer treated with first-line cetuximab and panitumumab: an Italian healthcare payer perspective
Presenter: Karl Patterson
Session: Poster Display session 2
Resources:
Abstract