At the AGORA Cancer Research Center, we are exploring the immune ecosystem of thoracic cancers, during tumor growth and in response to treatment. Our structure results from an outstanding union of two complementary research laboratories, the Meylan and Perentes groups, who combine expertise in immuno-oncology and translational science. Together, we seek to elucidate key molecular and immune-mediated mechanisms that dictate disease progression and therapeutic response with in-depth investigations from mouse models and clinical patient samples. Our ultimate goal is to push the current boundaries of knowledge and pave the way for innovative therapeutic strategies that will improve the efficacy of current treatments and patient outcomes.
The immunometabolic response of thoracic malignancies
Lung cancer is the leading cause of cancer deaths worldwide in both women and men. Non-small-cell lung cancer (NSCLC) accounts for 80% of all lung cancer cases, with adenocarcinoma (LUAD) being the major subtype. General failure of response to conventional therapies, a limited number of treatment options, and diagnosis at a late stage are all hallmarks of this devastating disease. Hence, a better understanding of lung cancer is greatly needed.
From our recently published and unpublished findings, we are developing two principal research axes:
1) Therapy-mediated immune response in pleural carcinosis.
Locoregional therapies such as photodynamic therapy (PDT) and hyperthermic intrathoracic chemotherapy (HITOC) have shown promising response in pleural cancers. Initially developed to eliminate residual tumor cells following cytoreductive surgery, their immunomodulatory effects have received comparatively little attention until recently.
In murine models of pleural carcinosis, we identified that both approaches could profoundly reshape the tumor-associated immune signature and promote response to immune checkpoint blockade (CIR 2025 ; JITC 2025). From our initial preclinical findings, a phase I clinical trial has been initiated in patients with pleural carcinosis, for evaluation of pressurized intrathoracic aerosol cisplatin (PITHAC) administration. Based on our discoveries, we want now to decipher the mechanisms underlying the initiation of an effective anti-tumor immune control, and how they could be harnessed for an optimal response to existing immunotherapies.
2) Perturbations and functions of neutrophils.
Long overlooked in the field of cancer, neutrophils, their complex regulations, and their functions have recently begun to emerge. In non-small cell lung cancer, we demonstrated that neutrophils are altered upon tumor homing, with tumor-associated neutrophils (TAN) exhibiting increased glycolytic metabolism and survival capacity, two key parameters that contribute to their tumor support (CanRes 2021 ; EMBOMM 2024). Now we want to interrogate more globally, but also in greater detail, the metabolic and functional disturbances of neutrophils during cancer progression to advanced stage, including in pleural carcinosis, and during response to local or systemic treatments.
We hope our findings will help identify new vulnerabilities of tumor-supporting neutrophils that can be exploited clinically.
