Répondre au changement climatique par l’évaluation et la réduction des émissions de gaz à effet de serre à Paris

La question du changement climatique est une question de pollution globale. La mise en œuvre de solutions pratiques suppose un délicat jeu d’échelle, une articulation complexe entre politiques nationales et enjeux locaux. En France, le secteur du résidentiel/tertiaire (autrement dit : des logements et des bureaux) possède des potentiels de réduction des émissions de gaz à effet de serre importants. L’étude de l’Apur (Atelier parisien d’urbanisme) propose d’étudier cette question à l’échelle d..

Canicule à Paris et changement climatique : approche pluridisciplinaire de la vulnérabilité et de l’adaptation

International audienc

Le changement en environnement

Un concept-valise ? Une auberge espagnole ? Un lieu commun médiatique ? Un sujet de société ? Un nouvel objet scientifique ? Une figure de l’angoisse sociale ? Quelle est la part de la réalité et quelle est celle de nos représentations collectives ? Faut-il en attendre des bénéfices ou faudra-t-il en supporter les inconvénients ? À quels coûts et pour qui ? Qu’est-ce donc que le changement ? Qu’est-ce que le changement environnemental en particulier ? Anticiper, agir, réagir, pour ne pas subir..

BCG therapy downregulates HLA-I on malignant cells to subvert antitumor immune responses in bladder cancer

International audiencePatients with high-risk, nonmuscle-invasive bladder cancer (NMIBC) frequently relapse after standard intravesical bacillus Calmette-Guérin (BCG) therapy and may have a dismal outcome. The mechanisms of resistance to such immunotherapy remain poorly understood. Here, using cancer cell lines, freshly resected human bladder tumors, and samples from cohorts of patients with bladder cancer before and after BCG therapy, we demonstrate 2 distinct patterns of immune subversion upon BCG relapse. In the first pattern, intracellular BCG infection of cancer cells induced a posttranscriptional downregulation of HLA-I membrane expression via inhibition of autophagy flux. Patients with HLA-I–deficient cancer cells following BCG therapy had a myeloid immunosuppressive tumor microenvironment (TME) with epithelial-mesenchymal transition (EMT) characteristics and dismal outcomes. Conversely, patients with HLA-I–proficient cancer cells after BCG therapy presented with CD8+ T cell tumor infiltrates, upregulation of inflammatory cytokines, and immune checkpoint–inhibitory molecules. The latter patients had a very favorable outcome. We surmise that HLA-I expression in bladder cancers at relapse following BCG does not result from immunoediting but rather from an immune subversion process directly induced by BCG on cancer cells, which predicts a dismal prognosis. HLA-I scoring of cancer cells by IHC staining can be easily implemented by pathologists in routine practice to stratify future treatment strategies for patients with urothelial cancer. Copyright

Neuropilin-1 cooperates with PD-1 in CD8+ T cells predicting outcomes in melanoma patients treated with anti-PD1

International audienceTargeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by restoring antitumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Neuropilin-1 (NRP1) is a transmembrane glycoprotein required for nervous system and angiogenesis embryonic development, also expressed in immune cells. We hypothesized that NRP1 could be an immune checkpoint co-receptor modulating CD8+ T cells activity in the context of the antitumor immune response. Here, we show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T cells, cooperates and enhances PD-1 activity. In mice, CD8+ T cells specific deletion of Nrp1 improves anti-PD1 antibody antitumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T cells predicts poor outcome of patients treated with anti-PD1. NRP1 is a promising target to overcome resistance to anti-PD1 therapies