Franche Comté Électronique Mécanique Thermique et Optique Sciences et Technologies

About: Franche Comté Électronique Mécanique Thermique et Optique Sciences et Technologies is a facility organization based out in Besançon, France. It is known for research contribution in the topics: Resonator & Computer science. The organization has 1298 authors who have published 1699 publications receiving 26835 citations.

Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells

Abstract: Myeloid-derived suppressor cells (MDSCs) have been identified in humans and mice as a population of immature myeloid cells with the ability to suppress T cell activation. They accumulate in tumor-bearing mice and humans and have been shown to contribute to cancer development. Here, we have isolated tumor-derived exosomes (TDEs) from mouse cell lines and shown that an interaction between TDE-associated Hsp72 and MDSCs determines the suppressive activity of the MDSCs via activation of Stat3. In addition, tumor-derived soluble factors triggered MDSC expansion via activation of Erk. TDE-associated Hsp72 triggered Stat3 activation in MDSCs in a TLR2/MyD88-dependent manner through autocrine production of IL-6. Importantly, decreasing exosome production using dimethyl amiloride enhanced the in vivo antitumor efficacy of the chemotherapeutic drug cyclophosphamide in 3 different mouse tumor models. We also demonstrated that this mechanism is relevant in cancer patients, as TDEs from a human tumor cell line activated human MDSCs and triggered their suppressive function in an Hsp72/TLR2-dependent manner. Further, MDSCs from cancer patients treated with amiloride, a drug used to treat high blood pressure that also inhibits exosome formation, exhibited reduced suppressor functions. Collectively, our findings show in both mice and humans that Hsp72 expressed at the surface of TDEs restrains tumor immune surveillance by promoting MDSC suppressive functions.

Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth

Abstract: Chemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the release of cathepsin B, which bound to Nlrp3 and drove caspase-1 activation. MDSC-derived IL-1β induced secretion of IL-17 by CD4(+) T cells, which blunted the anticancer efficacy of the chemotherapy. Accordingly, Gem and 5FU exerted higher antitumor effects when tumors were established in Nlrp3(-/-) or Casp1(-/-) mice or wild-type mice treated with interleukin-1 receptor antagonist (IL-1Ra). Altogether, these results identify how activation of the Nlrp3 inflammasome in MDSCs by 5FU and Gem limits the antitumor efficacy of these chemotherapeutic agents.

Three-dimensional mechanical metamaterials with a twist

Abstract: Rationally designed artificial materials enable mechanical properties that are inaccessible with ordinary materials. Pushing on an ordinary linearly elastic bar can cause it to be deformed in many ways. However, a twist, the counterpart of optical activity in the static case, is strictly zero. The unavailability of this degree of freedom hinders applications in terms of mode conversion and the realization of advanced mechanical designs using coordinate transformations. Here, we aim at realizing microstructured three-dimensional elastic chiral mechanical metamaterials that overcome this limitation. On overall millimeter-sized samples, we measure twists per axial strain exceeding 2°/%. Scaling up the number of unit cells for fixed sample dimensions, the twist is robust due to metamaterial stiffening, indicating a characteristic length scale and bringing the aforementioned applications into reach.