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
5052 - Identification of first-in-class, naturally occurring LAG3 checkpoint inhibitor
Presenter: Gennady Bratslavsky
Session: Poster Display session 1
Resources:
Abstract
5336 - Are Epigenetic therapies modifying sensitivity to conventional chemotherapy?
Presenter: Alexandra Bizot
Session: Poster Display session 1
Resources:
Abstract
5739 - Oncogenic mutations at the dimer interface of EGFR lead to formation of covalent homo-dimers and allosteric activation of the kinase domain: A mechanism which alters the selectivity profile of oncogenic EGFR.
Presenter: Elizabeth Buck
Session: Poster Display session 1
Resources:
Abstract
5492 - Basic selective estrogen receptor degraders (B-SERDs) in combination with novel BET inhibitors in ER+ breast cancer
Presenter: Rui Xiong
Session: Poster Display session 1
Resources:
Abstract
5965 - EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer
Presenter: Ronan Le Moigne
Session: Poster Display session 1
Resources:
Abstract
3582 - AVID200 neutralizes TGF-beta1 and -beta3, the principal immunosuppressive TGF-beta isoforms overexpressed by tumors, and sensitizes tumors to immune checkpoint inhibitors.
Presenter: Tina Gruosso
Session: Poster Display session 1
Resources:
Abstract
1996 - High NAMPT expression and anti-tumor activity of NAMPT inhibitor in adult T-cell leukemia/lymphoma
Presenter: Tomohiro Kozako
Session: Poster Display session 1
Resources:
Abstract
4307 - TPX-0046 is a novel and potent RET/SRC inhibitor for RET-driven cancers
Presenter: Alexander Drilon
Session: Poster Display session 1
Resources:
Abstract
4869 - In Vivo Evaluation of Cisplatin-loaded PEG-PCL Block Copolymeric Nanoparticles for Anticancer Drug Delivery
Presenter: Yingtzu Yen
Session: Poster Display session 1
Resources:
Abstract
5054 - Inhibition of Rspo-Wnt pathway Facilitates Checkpoint Blockade Therapy by anti-RSPO3 antibody (DBPR117)
Presenter: John Hsu
Session: Poster Display session 1
Resources:
Abstract