Abstract 73P
Background
Although immunotherapy (IO) offers significant advances in the clinical management of NonSmall Cell Lung Cancer (NSCLC), durable benefits are not achieved in all patients. Mechanisms of resistance to IO in NSCLC are complex, mainly comprising tumor and infiltrating immune cells. However, resistance landscape against PD-1 blockade remains unclear. More recently, some evidence has provided evidence for metformin overcoming primary resistance to PD-1 inhibitor in mutant NSCLC models. Considering this, we aimed to assess the impact of the combined treatment of metformin plus atezolizumab on antitumor immune response from NSCLC patients-derived peripheral blood immune cells (PBMCs).
Methods
mRNA and protein expression of cGAS-STING downstream pathway and monocyte M1 marker levels were measured in PBMCs from NSCLC patients. MTS assay was used to assess cell viability of NSCLC cell lines co-cultured with PBMCs or monocyte-conditioned medium. Evaluation of senescence phenotype was also performed based on a histochemical stain for the detection of β-galactosidase activity. Colony-forming ability of NSCLC cell lines co-cultured with immune cells derived from NSCLC patients (pre-treated with metformin 2 mM + atezolizumab 10 μg/ml for 48h) was also assessed.
Results
Metformin ± atezolizumab was able to activate the cGAS-STING pathway in PBMC-derived lymphocytes from NSCLC patients and reduce in vitro cell viability of NSCLC cells in 2D co-culture. Colony formation ability of NSCLC cell lines was reduced by activated lymphocytes pre-treated with metformin ± atezolizumab. Evaluation of the senescent phenotype in PBMC-isolated monocytes showed the greatest reduction in blue staining in the presence of the combined treatments. We also observed a reduction in cell viability by MTS assay of NSCLC cells cultured with monocyte-conditioned media treated with metformin ± atezolizumab. Furthermore, we found increased levels of M1 markers (TNFα, IL1β) in monocytes treated with the combined therapy.
Conclusions
Our results provide a novel role for synergistic effects of metformin combined with IO in enhancing the anti-tumor activity of multiple immune cells subsets from NSCLC patients.
Editorial acknowledgement
NA
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
72P - Role of pyruvate carboxykinase 2 upregulation in group 3 medulloblastoma: Implications for metabolic reprogramming and therapeutic strategies
Presenter: MEDHA GAYATHRI PAI
Session: Cocktail & Poster Display session
Resources:
Abstract
74P - Obesity regulates tumor progression and sensitivity to checkpoint blockade through the diet-microbiota-immunity axis
Presenter: Lysanne Desharnais
Session: Cocktail & Poster Display session
Resources:
Abstract
75P - Possible significance of the proline at position 325 in the recognition of the MX35 epitope of the NaPi2b transporter by monoclonal antibodies
Presenter: Leisan Bulatova
Session: Cocktail & Poster Display session
Resources:
Abstract
76P - Circadian control of neutrophil extracellular trap formation temporally regulates metastatic lung cancer progression
Presenter: Simon Milette
Session: Cocktail & Poster Display session
Resources:
Abstract
78P - Daily rhythmic expression of pro-tumoral programs in NSCLC shape cancer immunity and therapy response
Presenter: Alba de Juan
Session: Cocktail & Poster Display session
Resources:
Abstract
79P - Tumor cell-released autophagosomes (TRAPs) remodel the breast tumor microenvironment by inducing the formation of inflammatory cancer-associated fibroblasts (CAFs)
Presenter: Chengdong Wu
Session: Cocktail & Poster Display session
Resources:
Abstract
80P - Tumor microenvironment (TME) defines prognosis of EGFR-mutant non-small cell lung cancer (NSCLC)
Presenter: Lodovica Zullo
Session: Cocktail & Poster Display session
Resources:
Abstract
81P - Single-cell spatial landscape of NSCLC reveals subtype specific immune features
Presenter: Mark Sorin
Session: Cocktail & Poster Display session
Resources:
Abstract
82P - Tumor cell-released autophagosomes (TRAPs) promote breast cancer lung metastasis by modulating neutrophil extracellular traps formation
Presenter: XIAOHE ZHOU
Session: Cocktail & Poster Display session
Resources:
Abstract
83P - Evaluation of serum macrophage inhibitory cytokine 1 as a diagnostic biomarker for pancreatic cancer: A systematic review and diagnostic accuracy meta-analysis
Presenter: Muhammed Elfaituri
Session: Cocktail & Poster Display session
Resources:
Abstract