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
84P - Profiling of lipid-loaded macrophages in melanoma
Presenter: Marta Pandini
Session: Cocktail & Poster Display session
Resources:
Abstract
85P - Whole-genome CRISPR screening identifies chemosensor receptors as key regulators of the cancer-macrophage crosstalk
Presenter: Giulia Marelli
Session: Cocktail & Poster Display session
Resources:
Abstract
86P - Regulation of cancer progression through the gut microbiome and immuno-nutrition
Presenter: Anikka Swaby
Session: Cocktail & Poster Display session
Resources:
Abstract
87P - Macrophage ontogeny underlies functional programs and drives brain tumor progression
Presenter: Miranda Yu
Session: Cocktail & Poster Display session
Resources:
Abstract
88P - Evaluating the infiltration of anti-NKG2DL CAR-T cells into a 3D cell culture developed in a Vitvo cartridge bioreactor
Presenter: Aigul Valiullina
Session: Cocktail & Poster Display session
Resources:
Abstract
89P - Immune homeostasis mediators and disease progression in chemotherapy-naïve and neoadjuvant chemotherapy treated gastric cancer patients
Presenter: Vasileia Kokala-Dimitropoulou
Session: Cocktail & Poster Display session
Resources:
Abstract
90P - Neutrophils as producers of endothelial growth factor in the progression of kidney cancer
Presenter: Ilseya Myagdieva
Session: Cocktail & Poster Display session
Resources:
Abstract
91P - The impact of the immunological context on outcomes of solid cancer patients treated with genotype-matched targeted therapies: A systematic review
Presenter: Omar Mubarak
Session: Cocktail & Poster Display session
Resources:
Abstract
92P - Reduction in the relative lymphocyte count as a predictive biomarker for serious immune-related adverse events in patients with metastatic non-small cell lung cancer on immunotherapy: Single institution experience
Presenter: Antoan Garev
Session: Cocktail & Poster Display session
Resources:
Abstract
93P - A new platform for fast-track molecular stratification of endometrial carcinomas enabling timely treatment decisions in precision oncology
Presenter: Susanne Walz
Session: Cocktail & Poster Display session
Resources:
Abstract