Tumor-Associated Macrophages in Bladder Cancer: Biological Role, Impact on Therapeutic Response and Perspectives for Immunotherapy.

Tumor-associated macrophages (TAMs) are one of the most abundant infiltrating immune cells of solid tumors. Despite their possible dual role, i.e., pro- or anti-tumoral, there is considerable evidence showing that the accumulation of TAMs promotes tumor progression rather than slowing it. Several strategies are being developed and clinically tested to target these cells. Bladder cancer (BCa) is one of the most common cancers, and despite heavy treatments, including immune checkpoint inhibitors (ICIs), the overall patient survival for advanced BCa is still poor. TAMs are present in bladder tumors and play a significant role in BCa development. However, few investigations have analyzed the effect of targeting TAMs in BCa. In this review, we focus on the importance of TAMs in a cancerous bladder, their association with patient outcome and treatment efficiency as well as on how current BCa treatments impact these cells. We also report different strategies used in other cancer types to develop new immunotherapeutic strategies with the aim of improving BCa management through TAMs targeting

Giant gravitons in AdS/CFT (I): matrix model and back reaction

In this article we study giant gravitons in the framework of AdS/CFT correspondence. First, we show how to describe these configurations in the CFT side using a matrix model. In this picture, giant gravitons are realized as single excitations high above a Fermi sea, or as deep holes into it. Then, we give a prescription to define quasi-classical states and we recover the known classical solution associated to the CFT dual of a giant graviton that grows in AdS. Second, we use the AdS/CFT dictionary to obtain the supergravity boundary stress tensor of a general state and to holographically reconstruct the bulk metric, obtaining the back reaction of space-time. We find that the space-time response to all the supersymmetric giant graviton states is of the same form, producing the singular BPS limit of the three charge Reissner-Nordstr\"om-AdS black holes. While computing the boundary stress tensor, we comment on the finite counterterm recently introduced by Liu and Sabra, and connect it to a scheme-dependent conformal anomaly.Comment: 28 pages, JHEP3 class. v2: typos corrected and references adde

Half-BPS Giants, Free Fermions and Microstates of Superstars

We consider 1/2-BPS states in AdS/CFT. Using the matrix model description of chiral primaries explicit mappings among configurations of fermions, giant gravitons and the dual-giant gravitons are obtained. These maps lead to a `duality' between the giant and the dual-giant configurations which is the reflection of particle-hole duality of the fermion picture. These dualities give rise to some interesting consequences which we study. We then calculate the degeneracy of 1/2-BPS states both from the CFT and string theory and show that they match. The asymptotic degeneracy grows exponentially with the comformal dimension. We propose that the five-dimensional single charge `superstar' geometry should carry this density of states. An appropriate stretched horizon can be placed in this geometry and the entropy predicted by the CFT and the string theory microstate counting can be reproduced by the Bekenstein-Hawking formula up to a numerical coefficient. Similar M-theory examples are also considered.Comment: 21 pages, v2:typos corrected and references adde

Immuno-Transcriptomic Profiling of Blood and Tumor Tissue Identifies Gene Signatures Associated with Immunotherapy Response in Metastatic Bladder Cancer.

Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical responses to immunotherapy. In this study, we used next-generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed to identify biomarkers associated with immunotherapy response and assess the potential application of simple non-invasive blood biomarkers as a therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICIs. Interestingly, in both, a common lymphocytic activation signature can be identified associated with the efficient response to immunotherapy, including a blood-specific CD8+ T cell activation/proliferation signature which predicts the immunotherapy response

Nucleon deformation in finite nuclei

The deformation of a nucleon embedded in various finite nuclei is considered by taking into account the distortion of the chiral profile functions under the action of an external field representing the nuclear density. The baryon charge distribution of the nucleon inside light, medium-heavy and heavy nuclei is discussed. The mass of the nucleon decreases as it is placed deeper inside the nucleus and reaches its minimum at the center of the nucleus. We discuss the quantization of non-spherical solitons and its consequences for the mass splitting of the delta states. We show that bound nucleons acquire an intrinsic quadrupole moment due to the deformation effects. These effects are maximal for densities of nuclei about \rho(R)\sim 0.3...0.35 \rho(0). We also point out that scale changes of the electromagnetic radii can not simply be described by an overall swelling factor.Comment: 29 pp, REVTeX, 8 figures, more detailed discussion on quantization and intrinsic quadrupole moments, references adde

Phenomenology of a Pseudo-Scalar Inflaton: Naturally Large Nongaussianity

Many controlled realizations of chaotic inflation employ pseudo-scalar axions. Pseudo-scalars \phi are naturally coupled to gauge fields through c \phi F \tilde{F}. In the presence of this coupling, gauge field quanta are copiously produced by the rolling inflaton. The produced gauge quanta, in turn, source inflaton fluctuations via inverse decay. These new cosmological perturbations add incoherently with the "vacuum" perturbations, and are highly nongaussian. This provides a natural mechanism to generate large nongaussianity in single or multi field slow-roll inflation. The resulting phenomenological signatures are highly distinctive: large nongaussianity of (nearly) equilateral shape, in addition to detectably large values of both the scalar spectral tilt and tensor-to-scalar ratio (both being typical of large field inflation). The WMAP bound on nongaussianity implies that the coupling, c, of the pseudo-scalar inflaton to any gauge field must be smaller than about 10^{2} M_p^{-1}.Comment: 45 pages, 7 figure

Atelier ludique

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Maf deficiency in T cells dysregulates T_reg - T_H17 balance leading to spontaneous colitis.

The maintenance of homeostasis in the gut is a major challenge for the immune system. Here we demonstrate that the transcription factor MAF plays a central role in T cells for the prevention of gastro-intestinal inflammation. Conditional knock out mice lacking Maf in all T cells developed spontaneous late-onset colitis, correlating with a decrease of FOXP3 <sup>+</sup> RORγt <sup>+</sup> T cells proportion, dampened IL-10 production in the colon and an increase of inflammatory T <sub>H</sub> 17 cells. Strikingly, FOXP3 <sup>+</sup> specific conditional knock out mice for MAF did not develop colitis and demonstrated normal levels of IL-10 in their colon, despite the incapacity of regulatory T cells lacking MAF to suppress colon inflammation in Rag1 <sup>-/-</sup> mice transferred with naïve CD4 <sup>+</sup> T cells. We showed that one of the cellular sources of IL-10 in the colon of these mice are T <sub>H</sub> 17 cells. Thus, MAF is critically involved in the maintenance of the gut homeostasis by regulating the balance between T <sub>reg</sub> and T <sub>H</sub> 17 cells either at the level of their differentiation or through the modulation of their functions

L’hypoxie tumorale des glioblastomes favorise la migration et la polarisation des macrophages de type M2

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Hypoxia induces a pro-tumoral inflammation in brain tumors

CERVOXYNational audienc