Abstract 37P
Background
Early-stage non-small cell lung cancer (NSCLC) has a 5-year survival rate of 63%. Current standards of care include surgery in the form of lobectomy or resection and stereotactic ablative radiotherapy (SABR). However, the current limitation of SABR is the moderate rates of reoccurrence in patients receiving treatment. We hypothesize that Neutrophil Extracellular Traps (NETs) may play a role in radio-resistance by decreasing T cell infiltration and activation in the tumor microenvironment.
Methods
The SABR-Bridge cohort is comprised of patients eligible for surgery that instead received neoadjuvant SABR followed by surgery 3-6 months later due to the SARS-COV-2 Pandemic. This cohort provides the unique ability to analyze changes in the microenvironment in non-responders after radiation. In addition, we use an orthotopic model of NSCLC with LLC1 cells injected into the left lung of wildtype or PAD4KO mice. Mice were then irradiated on day 7 and the tumor microenvironment was characterized with spectral flow cytometry and immunofluorescence spectroscopy.
Results
Result show that irradiated PAD4KO mice had significant decrease in both tumor volume and burden in comparison to controls. Further PD1+ CD8+ T cell infiltration in irradiated PAD4KO mice was significantly increased in comparison to controls. Survival analysis demonstrated that irradiated PAD4KO mice the received subsequent immonotherapy treatment had significantly better OS in comparison to wildtype controls.
Conclusions
It can be concluded that NETs play a role in radio resistance through decreasing T cell infiltration in a NSCLC orthotopic setting. Further, in PAD4KO preclinical models, adjuvant immunotherapy was more effective conferring greater OS. Future implications include the use of DNase or PAD4i to potentially increase radiation induced T cell infiltration in the context of adjuvant immune checkpoint-blockade therapy (ICI) in patient settings.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
CIHR.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
20P - Effects of <italic>Apis dorsata</italic> honey on the expression of selected CYP450, pro-apoptotic, and anti-apoptotic genes during induced cytotoxicity in cyclophosphamide-treated human lung carcinoma (A549) cells
Presenter: Jose Kenneth Narag
Session: Cocktail & Poster Display session
Resources:
Abstract
21P - Hsa_circ_0009061 inhibits the progression of bladder cancer through the miR-889-3p/CPEB3 axis
Presenter: Minkang Wu
Session: Cocktail & Poster Display session
Resources:
Abstract
22P - Exploring exportin-1 as a therapeutic vulnerability in lung squamous cell carcinoma
Presenter: Vidushi Durani
Session: Cocktail & Poster Display session
Resources:
Abstract
23P - Identification of HPSE as potential novel therapeutic target for lung adenocarcinoma patients
Presenter: Samuel Doré
Session: Cocktail & Poster Display session
Resources:
Abstract
24P - High-throughput plasma proteomics profiling in early breast cancer
Presenter: Isabella Lombardo
Session: Cocktail & Poster Display session
Resources:
Abstract
25P - Immunohistochemical analysis of ROR1 and BMI-1 expression in luminal breast cancer
Presenter: Sergey Vtorushin
Session: Cocktail & Poster Display session
Resources:
Abstract
26P - Associations between cancer stem cells (CSC) markers and androgen (AR) and estrogen (ER) receptors expression in prostate cancer (PCa)
Presenter: Marina Puchinskaya
Session: Cocktail & Poster Display session
Resources:
Abstract
27P - Proteomic profiling reveals organ-specific differences in metastases and identifies potential biomarkers for recurrence risk in localized colon cancer
Presenter: Blanca García-Micó
Session: Cocktail & Poster Display session
Resources:
Abstract
28P - Collagen-activated signalling pathway is significantly hypermethylated in high-grade serous ovarian cancer (HGSOC) patients treated with platinum-containing neoadjuvant chemotherapy (NACT)
Presenter: Jose Alejandro Perez Fidalgo
Session: Cocktail & Poster Display session
Resources:
Abstract
29P - Quantitative tissue analysis reveal adenylate kinase 2 protein signatures: Therapeutic target for meningioma
Presenter: Rashmi Rana
Session: Cocktail & Poster Display session
Resources:
Abstract