Current lab members:

• Paul HOFMAN (PUCE2-PH)
• Marius Ilié (PU1-PH)
• Charles Hugo Marquette (PU1-PH) Véronique Hofman (PH, MD, PhD)
• Elodie Long-Mira (MCU-PH, MD, PhD)
• Jean Philippe Berthet (PU2-PH)
• Lea Berland (PhD Student) (Dir P Hofman) Guylène Rignol (PhD Student) (Dir P Hofman) Samantha Goffinet (AHU, MD)
• Mathieu Garcia (Master 1) (Dir P Hofman)

• Valérie VOURET-CRAVIARI (DR2 CNRS, PhD, HDR)
• Marion Debeaud, Research engineer, 2023-2026 Sarah Belaid, Master 1, 2024
• Jonathan Benzaquen, MD PhD, CHU
• Thierry Juhel, TCH

• Patrick BREST (CRHC INSERM, PhD, HDR)
• Nesrine Rachedi, Postdoc, 2024-2027,
• Antonin Bourdin, Research engineer, 2024-2027,
• Victoria Nicolini, 4th year PhD student, 2021-2024,
• Amira Ouertani, 3rd year PhD student, 2022-2024 (Co-direction),
• Mathilde Dupart, 1st year PhD student, 2023-2025,
• Matthieu Post, Master 2, 2024.

• Baharia MOGRABI (CRCN INSERM, PhD, HDR)
• Amine BELAID, Postdoc, 2024-2029
• Tanguy AUDOIN, Master 2, 2024
• Jonas MEZIANE, Master 1, 2024
• Ambre PARAYRE, Master 1, 2024
• Barnabé ROMÉO, IE INSERM

Lab Alumni:

Our team is researching next-generation therapies for lung cancer, which remains the deadliest cancer globally despite the emergence of promising new treatments. The team is focused on determining the spectrum of genetic, non-genetic, and cellular events in lung cancer to better characterize the underlying mechanisms associated with non-therapeutic response, identify at baseline biomarkers for non-response to immunotherapies (and targeted therapies), and improve response to immunotherapies with the next-generation combination of molecules.

To achieve this goal, our team gathers 3 senior scientists and 7 pathologists and physicians working in 4 interconnected areas of research.

Team Leader Prof P. Hofman: Development of liquid biopsy for monitoring next generation immunotherapies in lung cancer (hofman.p@chu-nice.fr)

The Hofman Group aims to develop novel predictive biomarkers of ICI response (genetic, protein, tissue, circulating, and artificial intelligence-based) that can be rapidly translated to the clinic and ultimately be used to re-purpose approved therapeutics with ICIs.

Group Leader Dr V. Vouret-Craviari: Modulation of Purinergic Checkpoints as new immunotherapies in lung cancer (valerie.vouret@univ-cotedazur.fr)

The purinergic checkpoints (PC), comprising purinergic receptors, ectonucleotidases and adenosine receptors, are targetable proteins influencing the progression of lung cancer. The Vouret Group is studying how PC guide immune cells to anti-tumor responses using digital spatial profiling approaches, development of new tools to modulate PC and tumor organoids as preclinical models.

Group Leader Dr P. Brest: Membraneless biocondensates and mRNA translational regulation in lung cancer (patrick.brest@univ-cotedazur.fr)

The Brest Group is focusing on RNA-binding proteins (RBPs) within membraneless biocondensates, which trap untranslated and stored mRNAs, leading to a poor correlation between mRNA and protein levels. To efficiently cure patients, the Brest Group aims to comprehensively understand the mechanisms of mRNA translational regulations and develop genetic and pharmacological approaches to target biocondensates remodeling in tumors. They also aim to use RBPs as a therapeutic tool to target cancer. The Brest Group’s results suggest a paradigm change by focusing on the regulation of translation as the cornerstone of cancer resistance and aggressiveness. They aim to introduce RBPs and the RNA composition of biocondensates as a prognostic biomarker and propose potential treatments targeting them to prevent cancer resistance and dissemination.

Group Leader Dr B. Mograbi: Human endogenous retroviruses: Team Players in Combo to Boost Cancer Immunotherapy (Baharia.mograbi@univ-cotedazur.fr)

With the completion of the human genome sequence, human endogenous retroviruses (hERVs) emerge to occupy at least 9% of our genome. Overlooked as junk DNA, it is now well appreciated that we have domesticated the hERVs for maternal-fetal immune tolerance during embryogenesis (ENV proteins) or immune defense against infection (viral mimicry of dsRNA). However, hERVs are also re-expressed in all cancers, and controversy persists on their roles. The B MOGRABI group advocates that hERVs are our allies against cancer, which alarm our anti-tumor immune defenses by committing a complete interferon response from antigen presentation and lymphocyte infiltration to immune checkpoint expression. B MOGRABI group aims to clarify the basic mechanisms by which ERVs are regulated by autophagy.

Current Projects

Top Publications

• Impact of the Lung Microbiota on Development and Progression of Lung Cancer
  16 octobre 2024 par Amine Belaid
  The past several years have provided a more profound understanding of the role of microbial species in the lung. The respiratory tract is a delicate ecosystem of bacteria, fungi, parasites, and viruses. Detecting microbial DNA, pathogen-associated molecular patterns (PAMPs), and metabolites in sputum is poised to revolutionize the early diagnosis of lung cancer. The longitudinal monitoring of the lung microbiome holds the potential to predict treatment response and side effects, enabling more…
• Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors
  21 juin 2024 par Léa Berland
  The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular immune-checkpoint inhibitors (ICIs). These immunotherapies release the host's immune system against the tumor and have shown unprecedented durable remission for patients with cancers that were thought incurable, such as metastatic melanoma, metastatic renal cell carcinoma (RCC), microsatellite instability…
• c-Met immunohistochemistry as reflex test at diagnosis for non-small cell lung cancer: a real-world experience from a monocentric case series
  8 novembre 2023 par Christophe Bontoux
  CONCLUSIONS: Systematic c-Met testing in daily routine for NSCLC patients is feasible, highlighting a potential correlation with clinicopathological and molecular features.
• Characterisation of the protein expression of the emerging immunotherapy targets VISTA, LAG-3 and PRAME in primary uveal melanoma: insights from a southern French patient cohort
  20 octobre 2023 par Nuno Jorge Lamas
  Uveal melanoma (UM) is the most common intraocular tumour in adults, with dismal prognosis once metastases develop, since therapeutic options for the metastatic disease are ineffective. Over the past decade, novel cancer therapies based on immunotherapy have changed the landscape of treatment of different forms of cancer leading to many hopes of improvement in patient overall survival (OS). VISTA, LAG-3 and PRAME are novel promising targets of immunotherapy that have recently gained attention in…
• Prognostic Role of <em>KRAS G12C</em> Mutation in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
  14 octobre 2023 par Durgesh Wankhede
  KRAS G12C mutation (mKRAS G12C) is the most frequent KRAS point mutation in non-small cell lung cancer (NSCLC) and has been proven to be a predictive biomarker for direct KRAS G12C inhibitors in advanced solid cancers. We sought to determine the prognostic significance of mKRAS G12C in patients with NSCLC using the meta-analytic approach. A protocol is registered at the International Prospective Register for systematic reviews (CRD42022345868). PubMed, EMBASE, The Cochrane Library, and…
• Current challenges and practical aspects of molecular pathology for non-small cell lung cancers
  6 octobre 2023 par Paul Hofman
  The continuing evolution of treatment options in thoracic oncology requires the pathologist to regularly update diagnostic algorithms for management of tumor samples. It is essential to decide on the best way to use tissue biopsies, cytological samples, as well as liquid biopsies to identify the different mandatory predictive biomarkers of lung cancers in a short turnaround time. However, biological resources and laboratory member workforce are limited and may be not sufficient for the increased…
• Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
  25 septembre 2023 par Christophe Bontoux
  The number of molecular alterations to be tested for targeted therapy of non-squamous non-small cell lung cancer (NS-NSCLC) patients has significantly increased these last few years. The detection of molecular abnormalities is mandatory for the optimal care of advanced or metastatic NS-NSCLC patients, allowing targeted therapies to be administrated with an improvement in overall survival. Nevertheless, these tumors develop mechanisms of resistance that are potentially targetable using novel…
• Real-world EGFR testing practices for non-small-cell lung cancer by thoracic pathology laboratories across Europe
  15 septembre 2023 par P Hofman
  CONCLUSIONS: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe.
• The prognostic value of TMB in early-stage non-small cell lung cancer: a systematic review and meta-analysis
  5 septembre 2023 par Durgesh Wankhede
  CONCLUSION: The inherent prognostic role of TMB is limited in early-stage NSCLC. Ethnic differences in mutation burden must be considered while designing future trials on neoadjuvant immunotherapy. Further research in the harmonization and standardization of panel-based TMB is essential for its widespread clinical utility.Registration: CRD42023392846.
• The Need to Set up a Biobank Dedicated to Lymphoid Malignancies: Experience of a Single Center (Laboratory of Clinical and Experimental Pathology, University Côte d'Azur, Nice, France)
  29 juillet 2023 par Christophe Bontoux
  Several therapies to improve the management of lymphoma are currently being investigated, necessitating the development of new biomarkers. However, this requires high-quality and clinically annotated biological material. Therefore, we established a lymphoma biobank including all available biological material (tissue specimens and matched biological resources) along with associated clinical data for lymphoma patients diagnosed, according to the WHO classification, between 2005 and 2022 in the…
• Assessment of Different Circulating Tumor Cell Platforms for Uveal Melanoma: Potential Impact for Future Routine Clinical Practice
  14 juillet 2023 par Arnaud Martel
  Liquid biopsy and circulating tumor cell (CTC) screening has gained interest over the last two decades for detecting almost all solid malignancies. To date, the major limitation in terms of the applicability of CTC screening in daily clinical practice is the lack of reproducibility due to the high number of platforms available that use various technologies (e.g., label-dependent versus label-free detection). Only a few studies have compared different CTC platforms. The aim of this study was to…
• A Real-World Experience from a Single Center (LPCE, Nice, France) Highlights the Urgent Need to Abandon Immunohistochemistry for ROS1 Rearrangement Screening of Advanced Non-Squamous Non-Small Cell Lung Cancer
  27 mai 2023 par Véronique Hofman
  The detection of ROS1 rearrangements in metastatic non-squamous non-small cell lung carcinoma (NS-NSCLC) permits administration of efficient targeted therapy. Detection is based on a testing algorithm associated with ROS1 immunohistochemistry (IHC) screening followed by ROS1 FISH and/or next generation sequencing (NGS) to confirm positivity. However, (i) ROS1 rearrangements are rare (1-2% of NS-NSCLC), (ii) the specificity of ROS1 IHC is not optimal, and (iii) ROS1 FISH is not widely available,…
• Need for a Dedicated Ophthalmic Malignancy Clinico-Biological Biobank: The Nice Ocular MAlignancy (NOMA) Biobank
  16 mai 2023 par Arnaud Martel
  Ophthalmic malignancies include various rare neoplasms involving the conjunctiva, the uvea, or the periocular area. These tumors are characterized by their scarcity as well as their histological, and sometimes genetic, diversity. Uveal melanoma (UM) is the most common primary intraocular malignancy. UM raises three main challenges highlighting the specificity of ophthalmic malignancies. First, UM is a very rare malignancy with an estimated incidence of 6 cases per million inhabitants. Second,…
• Accurate Detection of SARS-CoV-2 by Next-Generation Sequencing in Low Viral Load Specimens
  25 février 2023 par Marius Ilié
  As new SARS-CoV-2 variants emerge, there is an urgent need to increase the efficiency and availability of viral genome sequencing, notably to detect the lineage in samples with a low viral load. SARS-CoV-2 genome next-generation sequencing (NGS) was performed retrospectively in a single center on 175 positive samples from individuals. An automated workflow used the Ion AmpliSeq SARS-CoV-2 Insight Research Assay on the Genexus Sequencer. All samples were collected in the metropolitan area of the…
• Determinants of humoral immune response to SARS-CoV-2 vaccines in solid cancer patients: A systematic review and meta-analysis
  15 février 2023 par Durgesh Wankhede
  CONCLUSION: Cytotoxic therapy for solid cancer may portend poor immune response following 2 doses of COVID-19 vaccines suggesting a need for booster doses in these patients. Immunotherapy and targeted therapy are likely to be associated with seropositive status, and thus can be considered as an alternative to cytotoxic agents in cases where both therapies are equally efficacious.
• Ultrafast Gene Fusion Assessment for Nonsquamous NSCLC
  31 janvier 2023 par Véronique Hofman
  CONCLUSIONS: UFGFA using NGS and reverse-transcriptase polymerase chain reaction approaches had an equal level of detection of gene fusion but with some technique-specific limitations. Nevertheless, UFGFA detection in routine clinical care is feasible with both systems allowing faster initiation of therapy and a broad degree of screening.
• Circulating Tumor Cells as a Predictive Biomarker in Resectable Lung Cancer: A Systematic Review and Meta-Analysis
  23 décembre 2022 par Durgesh Wankhede
  Background: In breast, prostate, and other epithelial tumors, circulating tumor cells (CTC) in peripheral blood may predict survival. Our study evaluated the prognostic significance of baseline and postoperative CTC in patients with early non-small cell lung cancer (NSCLC) through a meta-analytic approach. Methods: Prospective studies comparing survival outcomes between positive (CTC+) and negative CTC (CTC−) patients were systematically searched. Primary outcomes were overall (OS) and…
• Deciphering the Impact of <em>HER2</em> Alterations on Non-Small-Cell Lung Cancer: From Biological Mechanisms to Therapeutic Approaches
  27 octobre 2022 par Christophe Bontoux
  Despite the recent increase in the number of types of treatments, non-small-cell lung cancer (NSCLC) remains the major cause of death from cancer worldwide. So, there is an urgent need to develop new therapeutic strategies. The HER2 gene codes for tyrosine kinase receptor whose alterations are known to drive carcinogenesis. HER2 alterations, including amplification, mutations, and overexpression, have been mainly described in breast and gastric cancers, but up to 4% of NSCLC harbor actionable…
• The Third Joint Meeting on Lung Cancer of the FHU OncoAge (University Côte d'Azur, Nice, France) and the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Understanding New Therapeutic Options and Promising Predictive Biomarkers for Lung Cancer Patients
  9 septembre 2022 par Paul Hofman
  We are proud and happy to present this Special Issue, a follow-up to the third joint meeting on lung cancer of the FHU OncoAge (University Côte d'Azur, Nice, France) and the University of Texas MD Anderson Cancer Center (Houston, TX, USA), which was held virtually on 4 October 2021 […].
• Mutations in <em>KMT2C</em>, <em>BCOR</em> and <em>KDM5C</em> Predict Response to Immune Checkpoint Blockade Therapy in Non-Small Cell Lung Cancer
  10 juin 2022 par Dingxie Liu
  Efficient predictive biomarkers are urgently needed to identify non-small cell lung cancer (NSCLC) patients who could benefit from immune checkpoint blockade (ICB) therapy. Since chromatin remodeling is required for DNA repair process, we asked whether mutations in chromatin remodeling genes could increase tumor mutational burden (TMB) and predict response to ICB therapy in NSCLC. Analysis of seven ICB-treated NSCLC cohorts revealed that mutations of three chromatin remodeling-related genes,…

Lab News

Research Projects

Find out what projects IRCAN researchers are working on at the moment!

Platforms & Services

Find out about our platforms and services that drive our research.

Research Teams

IRCAN has a diverse research teams, tackling a wide range and resolution of topics in ageing and cancer.