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
3690 - PD-L1 expression in resected undifferentiated pleomorphic sarcoma and its clinical implications
Presenter: Kyoungmin Lee
Session: Poster Display session 1
Resources:
Abstract
2013 - PD-L1 expression as a potential therapeutic target and prognostic biomarker in well-differentiated and dedifferentiated liposarcoma.
Presenter: Heejung Chae
Session: Poster Display session 1
Resources:
Abstract
5021 - Soft tissue sarcomas express a distinct mRNA immune profile
Presenter: Viktor Grünwald
Session: Poster Display session 1
Resources:
Abstract
3029 - The molecular landscape of fusion genes in endometrial stromal sarcomas include three nosological entities with different natural history
Presenter: Mehdi Brahmi
Session: Poster Display session 1
Resources:
Abstract
3914 - Clinical validation of a novel assay for the detection of diagnostic alterations in sarcomas
Presenter: Lauren Mc Connell
Session: Poster Display session 1
Resources:
Abstract
1912 - A prospective correlative trial of personalized patient-derived xenograft (PDX) as avatars for drug therapy in patients with metastatic or recurrent soft tissue sarcomas (STS).
Presenter: Kanan Alshammari
Session: Poster Display session 1
Resources:
Abstract
5097 - Fusion of immortalized myoblasts induces genomic instability that drives tumor development and progression.
Presenter: Candice Merle
Session: Poster Display session 1
Resources:
Abstract
1383 - let-7a suppress Ewing sarcoma CSCs' malignant phenotype through forms a positive feedback regulation loop with lin28 via STAT3
Presenter: Xu Jiang
Session: Poster Display session 1
Resources:
Abstract
3386 - Myoepithelial Tumors of Soft Tissues and Extraskeletal Myxoid Chondrosarcomas feature a distinct transcriptional pattern
Presenter: Dominga Racanelli
Session: Poster Display session 1
Resources:
Abstract
1844 - In Vivo Efficacy and Enhanced Tumor Accumulation of Liposomal Vinorelbine (TLC178) in Human Sarcoma Xenograft Mice Model
Presenter: Wan-ni Yu
Session: Poster Display session 1
Resources:
Abstract