Abstract 4925
Background
CD73 is an enzyme involved in the conversion of extracellular AMP into adenosine. Adenosine inhibits T lymphocytes, contributing to immune escape. CD73 promotes proliferation and migration and has been associated to a negative prognosis in various cancers. Data are limited on its role in metastatic NSCLC, particularly with genetic drivers.
Methods
We collected patients (pts) with EGFR Mutant (EM), ALK Rearranged (AR) and Wild Type (WT) metastatic NSCLC treated outside trials at our Institution between 2010 and 2018. Cases without tissue samples were excluded. CD73 expression was determined by immunohistochemistry (Ab133582 ABCAM). Semiquantitative H score (HS) was calculated multiplying the membrane intensity score (0-3) by the % of stained cells to yield a value of 0–300. Median value of HS was chosen as a cutoff. Overall Survival (OS) was estimated through Kaplan-Meier method. After a gene expression profiling on TCGA NSCLC datasets (n = 488), we divided EM, AR, WT cases according to CD73 median level. Cibersort analysis was performed in these series to profile the immune infiltrate.
Results
Fifty-four EM, 28 AR and 40 WT NSCLCs were identified. Median HS was 0 for EM and WT, 100 for AR cases. No imbalances in CD73 expression emerged according to main clinico-pathological variables. EM pts with a high HS showed a trend towards a worse OS (23.4 vs 39.5 months, p .2237); on the contrary, high HS had a non-significant positive prognostic role in AR (53.3 vs 25.1 months, p .1263) and WT pts (59.6 vs 18.7 months, p .5063). In accordance with our data, we observed some differences among the CD73 high subgroups profiling infiltrate of TCGA cases: WT were enriched in Treg and resting dendritic cells (DC), AR showed an increase in M1 macrophages, EM had a reduction in activated NK cells along with an increase in activated DC. Nanostring is ongoing on our series.
Conclusions
CD73 expression seems to have a different prognostic role for EM, AR and WT metastatic NSCLC. In particular, the trend towards a better outcome for AR cohort is a novel finding, potentially supported by a specific inflammatory infiltrate. Despite the small number of analyzed cases, CD73 role in NSCLC different subgroups warrants further investigation. Nanostring results will be presented.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. Lo Russo: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly. D. Signorelli: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS. F.G.M. de Braud: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer-Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: F. Hoffmann-La Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Ignyta; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer. M.C. Garassino: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): MSD International GmbH; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Boehringer Ingelheim Italia S.p.A; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Ignyta; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Incyte; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Inivata; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): MedImmune; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Takeda; Honoraria (institution), Research grant / Funding (institution): Tiziana; Honoraria (institution), Research grant / Funding (institution): Foundation Medicine; Research grant / Funding (self): AIRC; Honoraria (institution): AIFA; Honoraria (institution): Italian Moh; Honoraria (institution): Transcan. C. Proto: Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (institution), Travel / Accommodation / Expenses: BMS; Honoraria (institution), Travel / Accommodation / Expenses: Eli Lilly. All other authors have declared no conflicts of interest.
Resources from the same session
2045 - The analysis of treatment sequences and clinical outcomes of thymic carcinoma
Presenter: Arakaki Motoko
Session: Poster Display session 1
Resources:
Abstract
4785 - Transcriptomic Difference of Thymoma and Thymic Carcinoma
Presenter: Naixin Liang
Session: Poster Display session 1
Resources:
Abstract
2864 - A Phase II Trial of Preoperative Chemoradiotherapy and Pembrolizumab for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Presenter: Seoyoung Lee
Session: Poster Display session 1
Resources:
Abstract
5015 - The study of tumor associated exosomes in crosstalk between esophageal carcinoma and lymphatic endothelial cells
Presenter: Weimin Mao
Session: Poster Display session 1
Resources:
Abstract
1339 - Up-regulation of IBSP expression predicts poor prognosis of Esophageal Squamous Cell Carcinoma patients
Presenter: Mingyue Wang
Session: Poster Display session 1
Resources:
Abstract
4083 - PD-L1 expression in primary tumour vs metastatic samples in the Phase 3 MYSTIC study in first-line metastatic (m) NSCLC
Presenter: Niels Reinmuth
Session: Poster Display session 1
Resources:
Abstract
5113 - Assessing the impact of subsequent checkpoint inhibitor (CPI) treatment on overall survival: post hoc analyses from the phase 3 JAVELIN Lung 200 study of avelumab vs docetaxel in platinum-treated locally advanced/metastatic non-small cell lung cancer (NSCLC)
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract
4256 - Long-term avelumab treatment in patients with advanced non-small cell lung cancer (NSCLC): post hoc analyses from JAVELIN Solid Tumor
Presenter: Borys Hrinczenko
Session: Poster Display session 1
Resources:
Abstract
4305 - Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: Updated survival and subgroup analysis from the real-world EVIDENS study
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract
5128 - IO-Synthesise NSCLC: A pooled analysis of real-world survival outcomes for non-small cell lung cancer patients treated with nivolumab in France and Germany
Presenter: Adrien Dixmier
Session: Poster Display session 1
Resources:
Abstract