Marco Alifano

Assistance Publique – Hôpitaux de Paris | AP-HP · Thoracic Surgery

Background Prognostic assessment in patients undergoing cancer treatments is of paramount importance to plan subsequent management. In resectable lung cancer availability of an easy-to use nomogram to predict long-term outcome would be extremely useful to identify high-risk patients in the era of perioperative targeted and immune therapies. Method...

Acetylcholine receptor (AChR) myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness. The AChR ⁺ autoantibodies are produced by B-cells located in thymic ectopic germinal centers (eGC). No therapeutic approach is curative. The inflammatory IL-23/Th17 pathway is activated in the thymus as well as in the blood and the...

On one hand, regulatory T cells (Tregs) play an immunosuppressive activity in most solid tumors but not all. On the other hand, the organization of tumor-infiltrating immune cells into tertiary lymphoid structures (TLS) is associated with long-term survival in most cancers. Here, we investigated the role of Tregs in the context of Non-Small Cell Lu...

Studies carried out in the last ten years have shown that the metabolites made up from the gut microbiota are essential for multiple functions, such as the correct development of the immune system of newborns, interception of pathogens, and nutritional enrichment of the diet. Therefore, it is not surprising that alteration of the gut microbiota is...

Background Obesity is a well-established risk factor for pancreatic cancer. Bariatric surgery has demonstrated superior results in terms of weight loss and obesity-related comorbidities compared to medical and behavioral treatments. The aim of this study is to evaluate the effect of bariatric surgery on pancreatic cancer incidence in individuals wi...

Résumé Les cancers bronchiques non-à-petites-cellules (CBNPC) de stades III doivent être séparés en stade IIIA qui représente un groupe hétérogène, et en stade IIIB et IIIC suivant la 8e édition de la classification TNM. L’atteinte N2 définit le sous-groupe du stade IIIA le plus fréquent mais également le plus hétérogène. Ce qui concerne le stade I...

Objectives Although critical in animal and human development and pathology, a measurement of the quantitative expression of 5-HTR serotonin receptors on animal or human valvular tissues has never been performed. Methods Quantification of the most frequent 5-HTRs reported as being present in human peripheral tissue was performed using radiolabeled...

Aspergillus fumigatus is a ubiquitous mold that can cause severe infections in immunocompromised patients, typically manifesting as invasive pulmonary aspergillosis (IPA). Adaptive and innate immune cells that respond to A. fumigatus are present in the endogenous repertoire of patients with IPA but are infrequent and cannot be consistently isolated...

NSCLC is the leading cause of cancer mortality and represents a major challenge in cancer therapy. Intrinsic and acquired anticancer drug resistance are promoted by hypoxia and HIF-1α. Moreover, chemoresistance is sustained by the activation of key signaling pathways (such as RAS and its well-known downstream targets PI3K/AKT and MAPK) and several...

Background: A prognostic score including T-dimension, age, histology and lymph node ratio was previously proposed in absence of an external validation dataset. The aim of the current study was to validate the proposed prognostic score using an independent dataset. Methods: Data of patients with lung carcinoids, who underwent surgical resection a...

PI3K/AKT is one of the most frequently altered signaling pathways in human cancers, supporting the activation of many proteins sustaining cell metabolism, proliferation, and aggressiveness. Another important pathway frequently altered in cancer cells is the one regulating the YAP/TAZ transcriptional coactivators, which promote the expression of gen...

Introduction SMARCA4/BRG1 loss of expression occurs in 5-10% of non-small cell lung carcinomas (NSCLC). We investigated the pathological, molecular and immune environment characteristics of this deficiency among NSCLC, its impact on overall survival (OS) of resected patients and the sensitivity to anti-PD1 inhibitors in metastatic patients. Materi...

Objective: To investigate risk factors for nodal upstaging in patients with lung carcinoids and to understand which type of lymphadenectomy is most appropriate. Methods: Data regarding patients with lung carcinoids, who underwent surgical resection and lymphadenectomy in five institutions from January 1, 2005 to December 31, 2019, were collected...

Introduction: In spite of increasing diffusion, Enhanced Recovery Pathways (ERP) have been scarcely assessed in large scale programs of lung cancer surgery. The aim of this study was auditing our practice. Methods: A two-step audit program was established: the first dealing with our initial ERP experience in patients undergoing non-extended anat...

Background Prediction of prognosis is a key step of malignant pleural mesothelioma (MPM) management and treatment assignment. Aim of this study was to identify simple prognostic factors, focusing on inflammation-related parameters. Methods baseline clinical and laboratory data were extracted from a single-center 20-year cohort of consecutive patie...

Surgery is the mainstay treatment of non-small-cell lung cancer (NSCLC), but its impact on very-long-term survival (beyond 15 years) has never been evaluated. Methods: All patients operated on for major lung resection (Jun. 2001-Dec. 2002) for NSCL in the Thoracic Surgery Department at Paris-Hôtel-Dieu-University-Hospital were included. Patients'...

Thoracic surgeons are familiar with the modes of diffusion of primary lung tumours; classically, nodal diffusion through the lymphatics and haematogenous metastases are recognized as the most frequent modes. They are known to determine outcomes and thus represent the basis of the tumour/node/metastasis staging system. Together with these diffusion...

Cardiac cells interact with the extracellular matrix (ECM) proteins through integrin mechanoreceptors that control many cellular events such as cell survival, apoptosis, differentiation, migration, and proliferation. Integrins play a crucial role in cardiac development as well as in cardiac fibrosis and hypertrophy. Integrins recognize oligopeptide...

Background: Survival rates among non-small cell lung cancer (NSCLC) stage IIIA (N2) patients are generally low and depend on the treatment. Patients and methods: We aimed to identify predictive markers for long term survival in responders and non-responders to chemotherapy, analyzing tumour and non-tumour samples by microarray (n=35) and whole e...

Introduction La sclérodermie systémique (ScS) est une connectivite responsable de pneumopathie interstitielle diffuse (PID). Il existe un sur-risque de cancer broncho pulmonaire (CBP) dans cette population et le traitement est à risque de complication (chirurgie sur PID, risque de décompensation de fibrose après radiothérapie ou immunothérapie). L’...

Citation: Schussler, O.; Falcoz, P.E.; Chachques, J.C.; Alifano, M.; Lecarpentier, Y. Possible Treatment of Myocardial Infarct Based on Tissue Engineering Using a Cellularized Solid Collagen Scaffold Functionalized with Arg-Glyc-Asp (RGD) Peptide. Int. J. Mol. Sci. 2021, 22, 12563. https://doi. Abstract: Currently, the clinical impact of cell thera...

In the frames of a One Health strategy, i.e. a strategy should be able to predict susceptibility to infection in both humans and animals, developing a SARS-CoV-2 mutation tracking system is a goal. We observed that the phylogenetic proximity of vertebrate ACE2 receptors does not affect the binding energy for the viral spike protein. However, all vi...

Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has shown remarkable clinical efficacy against advanced B-cell malignancies but not yet against solid tumors. Here, we used fluorescent imaging microscopy and ex vivo assays to compare the early functional responses (migration, Ca2+, and cytotoxicity) of CD20 and EGFR CAR T c...

Background: Immune checkpoint inhibitors (ICI) are dramatically active in a minority of non-small cell lung cancer (NSCLC) patients. We studied here the relationship between patients's metabolism and outcome under ICI. Methods: Metastatic NSCLC patients underwent a nutritional assessment prior to initiating immunotherapy. Resting energy expendit...

Autophagy is a self-degradative process important for balancing cellular homeostasis at critical times in development and/or in response to nutrient stress. This is particularly relevant in tumor model in which autophagy has been demonstrated to have an important impact on tumor behavior. In one hand, autophagy limits tumor transformation of precan...

Citation: Alifano, M.; Daffré, E.; Iannelli, A.; Brouchet, L.; Falcoz, P.E.; Le Pimpec Barthes, F.; Bernard, A.; Pages, P.B.; Thomas, P.A.; Dahan, M.; et al. The Reality of Lung Cancer Paradox: The Impact of Body Mass Index on Long-Term Survival of Resected Lung Cancer. A French Nationwide Analysis from the Epithor Database. Abstract: Obesity could...

COVID-19 pandemic has been characterized by a pattern of consecutive declines and regrowth in European countries in 2020. After being partially regressed during the summer, the reappearance of the infection during fall 2020 in many temperate countries strongly suggests that temperature and cold may play a role in influencing the infectivity and vir...

Background Surgical lung biopsy is essential in the diagnostic algorithm of interstitial lung disease (ILD) of unknown cause. Safety concerns have been recently reiterated. The aim of this study was to prospectively assess the yield of diagnosis and safety of video-assisted thoracoscopic surgical lung biopsy (VATS-LB) for ILD diagnosis. Methods Th...

Background Tumors rewire their metabolism to achieve robust anabolism and resistance against therapeutic interventions like cisplatin treatment. For example, a prolonged exposure to cisplatin causes downregulation of pyridoxal kinase (PDXK), the enzyme that generates the active vitamin B6, and upregulation of poly ADP-ribose (PAR) polymerase-1 (PAR...

The complement system is a powerful and druggable innate immune component of the tumor microenvironment. Nevertheless, it is challenging to elucidate the exact mechanisms by which complement affects tumor growth. In this study, we examined the processes by which the master complement regulator factor H (FH) affects clear cell renal cell carcinoma (...

Despite advances, malignant pleural mesothelioma (MPM) remains a challenging disease in terms of diagnosis, treatment, and overall management. Herein, we analyzed, in a large-scale single-center cohort, the characteristics and perioperative course of patients undergoing surgical diagnosis of MPM. We identified a total of 514 consecutive patients, 7...

Introduction: The use of Stereotactic Body Radiotherapy (SBRT) is controversial in Ultra-Central lung tumors, a subset of central lung tumors characterized by proximity to critical mediastinal structures. This is of interest in oligometastatic (≤3 metastases) patients, who can yield survival benefit from local treatments. The aim of our study is t...

We propose that fructose-1,6-bisphosphate (F-1,6-BP) promotes a feedback loop between phosphofructokinase-1 (PFK1), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and PFK2/PFKFB3, which enhances aerobic glycolysis and sustains effector T (Teff) cell activation, while oxidative metabolism is concomitantly downregulated. This regulation,...

Introduction: Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH) is a rare disease often associated with carcinoid tumors. We aimed at evaluating the impact of DIPNECH on characteristics and prognosis of patients who underwent radical treatment of pulmonary carcinoid tumors. Material and methods: We reviewed all patients oper...

Non-small cell lung cancer (NSCLC) accounts for approximately 27% of all cancer-related deaths worldwide, thus representing a major health problem [...]

There is no standardization in methods to assess sarcopenia; in particular the prognostic significance of muscular fatty infiltration in lung cancer patients undergoing surgery has not been evaluated so far. We thus performed several computed tomography (CT)-based morphometric measurements of sarcopenia in 238 consecutive non-small cell lung-cancer...

Background Infection of the pleural cavity invariably leads to hospitalisation, and a fatal outcome is not uncommon. Our aim was to study the epidemiology of pleural empyema on a nationwide basis in the whole population and in three subgroups of patients, namely post-lung resection, associated cancer and those with no surgery and no cancer. Method...

The presence of tertiary lymphoid structures (TLS) in the tumor microenvironment is associated with better clinical outcome in many cancers. In non-small cell lung cancer (NSCLC), we have previously showed that a high density of B cells within TLS (TLS-B cells) is positively correlated with tumor antigen-specific antibody responses and increased in...

This commentary addresses the need for novel endpoints in clinical research to assess the added value of local treatment of metastases in oligometastatic patients and in patients experiencing limited metastatic progression during systemic therapy (oligoprogressive). Novel metrics are proposed for future implementation in clinical trials.

Influenza virus infection leads to severe and complicated disease, particularly in patients with lung cancer. It alters the tumor microenvironment (TME), which may potentiate lung cancer progression and disrupt responses to antitumoral treatments. Consequently, influenza vaccination and antiviral treatments should be recommended to all patients wit...

Currently, the clinical impact of cell therapy after a myocardial infarction (MI) is limited by low cell engraftment due to significant cell death, including apoptosis, in an infarcted, inflammatory, poor angiogenic environment, low cell retention and secondary migration. Cells interact with their environment through integrin mechanoreceptors that...

The tumor microenvironment is a complex mix of cancerous and noncancerous cells (especially immune cells and fibroblasts) with distinct metabolisms. These cells interact with each other and are influenced by the metabolic disorders of the host. In this review, we discuss how metabolic pathways that sustain biosynthesis in cancer cells could be targ...

There is increasing evidence that ACE2 gene polymorphism can modulate the interaction between ACE2 and the SARS-CoV-2 spike protein affecting the viral entry into the host cell, and/or contribute to lung and systemic damage in COVID-19. Here we used in silico molecular docking to predict the effects of ACE2 missense variants on the interaction with...

Variants of SARS-CoV-2 have been identified rapidly after the beginning of pandemic. One of them, involving the spike protein and called D614G, represents a substantial percentage of currently isolated strains. While research on this variant was ongoing worldwide, on December 20th 2020 the European Centre for Disease Prevention and Control reported...

Introduction L’implémentation des programmes de récupération rapide après chirurgie (RRAC) a considérablement amélioré les suites opératoires du cancer du poumon. Les facteurs de risque dans ces conditions restent à élucider. Méthodes Une étude prospective mono-centrique a été menée sur les patients opérés d’un cancer pulmonaire dans une période d...

Introduction L’élargissement des indications d’inhibiteurs de check-point immunitaires comme le nivolumab, dans le traitement du cancer bronchopulmonaire non à petites cellules (CBNPC), entraîne un nombre croissant d’effets secondaires. Dans cette étude, nous avons évalué l’impact du nivolumab sur le diamètre de l’artère pulmonaire brut (PAD) et no...

Introduction En mars 2020, la France est entrée dans la phase 3 de la pandémie de SRAS-CoV-2 (COVID-19) conduisant à des mesures de santé publique comme le confinement et a engendré une profonde réorganisation des systèmes de soins, notamment en Ile de France. La redistribution des ressources matérielles et humaines vers la prise en charge de patie...

Résumé La prise en charge pathologique des pièces de résections chirurgicales de cancer du poumon après thérapie néo- adjuvante a eu récemment un regain d’intérêt avec l’émergence d’essais évaluant l’efficacité de l’immunothérapie en situation néoadjuvante. Dans ce contexte, l’international association for the study of lung cancer (IASLC) a publié...

Résumé La chirurgie est le traitement de référence des CBNPC de stades I, II et IIIA. Plusieurs essais randomisés de phase III de chimiothérapie adjuvante ou néoadjuvante avec une chimiothérapie à base de platine ont été menés dans les cancers de stades I, II et IIIA. Ces essais ont démontré un gain de survie significatif de la chimiothérapie adjuv...

Current mortality due to the Covid-19 pandemic (approximately 1.2 million by November 2020) demonstrates the lack of an effective treatment. As replication of many viruses - including MERS-CoV - is supported by enhanced aerobic glycolysis, we hypothesized that SARS-CoV-2 replication in host cells (especially airway cells) is reliant upon altered gl...

Objectives Sarcopenia is associated with poor outcome in cancer-patients. However, the methods to define sarcopenia are not entirely standardized. We compared several morphometric measurements of sarcopenia and their prognostic value in short-term-outcome prediction after pneumonectomy. Material and Methods Consecutive lung-cancer patients undergo...

Background: Coronavirus Disease 2019 (COVID-19) outbreak was officially declared in France on March 14th 2020. The objective of this study is to report the incidence and outcome of COVID-19 following surgical resection of non-small cell lung cancer (NSCLC) in Paris Public Hospitals during the pandemic. Methods: We retrospective analyzed a prospect...

Backgroung: Natural Killer (NK) cells play a crucial role in tumor immunosurveillance through their cytotoxic effector functions and their capacity to interact with other immune cells to build a coordinated antitumor immune response. Emerging data reveal NK cell dysfunction within the tumor microenvironment through checkpoint inhibitory molecules a...

Purpose: The widespread use of Nivolumab results in an increasing number of side effects and adverse events. Herein, we evaluated the impact of Nivolumab on crude and normalized pulmonary artery diameter (PAD). Methods: We analyzed clinical, morphometric, pathological and radiological data of lung cancer patients treated by Nivolumab in an 18-mo...

Résumé Plus de 80 % des cancers du poumon sont diagnostiqués à un stade avancé ou disséminé allant du stade IIB au stade IV du fait d’une maladie longtemps asymtomatique et de l’absence de dépistage. Le sous-groupe localement avancé relève éventuellement d’une chirurgie dont le pronostic s’est considérablement amélioré depuis l’optimisation du stag...

Background/aim: Patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) with no progression after induction chemotherapy are usually selected for surgery. Nowadays, response to chemotherapy is not predictable. We aimed to identify genomic predictive markers for response to induction chemotherapy in stage IIIA (N2) NSCLC patients. Patient...

p>Background: radiotherapy is a standard of care for locally advanced stage III (N2) non-small cell lung cancer (NSCLC) combined with surgery and/or chemotherapy. Radiotherapy is hypothesized to induce intra-tumoral immune infiltration via neoantigen release from dying tumor cells sometimes resulting in an abscopal effect. However, intra-tumoral im...

Background Radiotherapy is a standard of care for locally advanced stage III N2 non–small-cell lung carcinoma (NSCLC) combined with surgery/chemotherapy. Radiotherapy is hypothesised to induce tumour immunogenic cell death, to release neoantigen resulting in intra-tumoural immune infiltration and abscopal effect. Conversely, it has not been demonst...

Résumé Les adénocarcinomes du poumon présentent des réarrangements chromosomiques touchant les gènes ALK, ROS1, NTRK et RET dans 5 à 10 % des cas. Ces réarrangements sont associés à la production de transcrits de fusion, aboutissant à la synthèse de protéines chimériques ayant une activité kinase constitutive. Ces protéines anormales induisent une...

Purpose: To determine the risk of invasive mechanical ventilation and death in obese individuals with history of bariatric surgery compared to standard ones admitted for Covid-19 infection. Methods: Nationwide retrospective observational study based on electronic health data. 4 248 253 individuals aged 15 to 75 years with a diagnosis of obesity wer...

Résumé Une adaptation des thérapeutiques et une prise en charge personnalisée des patients atteints d’un cancer bronchique non à petites cellules opérable représentent ces dernières années un enjeu majeur. Ceci passe par une intégration de plusieurs paramètres dans la prise en charge du patient, pas uniquement les résultats histologiques, mais égal...

Hypothesizing that pulmonary artery diameter is a marker of subclinical pulmonary hypertension, we assessed its impact on postoperative outcome in patients requiring pneumonectomy. Morphometric, clinical, and laboratory data were retrospectively retrieved from files of 294 consecutive patients treated by pneumonectomy for malignancy (289 NSCLC). Pu...

Caloric starvation, as well as various diets, has been proposed to increase the oxidative DNA damage induced by radiotherapy (RT). However, some diets could have dual effects, sometimes promoting cancer growth, whereas proposing caloric restriction may appear counterproductive during RT considering that the maintenance of weight is a major factor f...

Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has shown remarkable clinical efficacy against advanced B cell malignancies but not yet against solid tumors. Here, we used fluorescent imaging microscopy and ex vivo assays to compare the early functional responses (migration, Ca2+, and cytotoxicity) of CD20 and EGFR CAR T c...