CRCL

Following the administration of immune checkpoint inhibitors, an unexpected pattern of response designated as hyperprogression may be observed in certain patients. This paradoxical response corresponds to an acceleration in tumor growth and a dramatic decrease of patient survival. The reported incidence rates of hyperprogressive disease are highly variable, ranging between 4 and 29%. In this review, we have performed a literature search on hyperprogressive disease, including both retrospective studies and case reports, and discuss potential predictive biomarkers as well as potential mechanisms associated with immune-checkpoint inhibitor associated hyperprogression.

Immune checkpoint inhibitors (ICI), such as anti-PD1 or anti-PDL1 antibodies, are one of the most important recent breakthroughs in oncology. These molecules have a double originality: on one hand they stimulate the patient’s immune system antitumor activity, and on the other they are not specific of a tumor antigen and therefore can be efficient in multiple types of cancer. Unfortunately, resistance to these therapies has increasingly been observed and needs to be better understood.

Toll-like receptor 3 (TLR3) is a pattern recognition receptor mainly known for its role in innate immune response to infection. Indeed, binding of double-stranded RNA (dsRNA) to TLR3 triggers a pro-inflammatory cascade leading to cytokine release and immune cell activation. Its anti-tumoral potential has emerged progressively, associated with a direct impact on tumor cell death induction and with an indirect action on immune system reactivation. Accordingly, TLR3 agonists are currently being tested in clinical trials for several adult cancers. Meanwhile, TLR3 variants have been linked to auto-immune disorders, and as risk factors of viral infection and cancers. However, aside from neuroblastoma, TLR3 role in childhood cancers has not been evaluated. Here, by integrating public transcriptomic data of pediatric tumors, we unveil that high TLR3 expression is largely associated with a better prognosis in childhood sarcomas. Using osteosarcomas and rhabdomyosarcomas as models, we show that TLR3 efficiently drives tumor cell death in vitro and induces tumor regression in vivo. Interestingly, this anti-tumoral effect was lost in cells expressing the homozygous TLR3 L412F polymorphism, which is enriched in a rhabdomyosarcomas cohort. Thus, our results demonstrate the therapeutic potential associated with the targeting of TLR3 in pediatric sarcomas, but also the need to stratify patients eligible for this clinical approach with respect to the TLR3 variants expressed.

Histological analysis is the gold standard method for cancer diagnosis. However, it is prone to subjectivity and sampling bias. In response to these limitations, we introduce a quantitative bimodal approach that aims to provide non-invasive guidance towards suspicious regions. Light backscattering spectroscopy and quantitative ultrasound techniques were combined to characterize two different bone tumor types from animal models: chondrosarcomas and osteosarcomas. Two different cell lines were used to induce osteosarcoma growth. Histological analyses were conducted to serve as references. Three ultrasound parameters and intensities of the light reflectance profiles showed significant differences between chondrosarcomas and osteosarcomas at the 5% level. Likewise, variations in the same biomarkers were reported for the two types of osteosarcoma, despite their similar morphology observed in the histological examinations. These observations show the sensitivity of our techniques in probi...

Qu'est-ce que la maladie et quelle est la valeur d'usage d'une telle notion ? Nous proposons dans ce travail d'explorer trois dimensions de la maladie que sont la construction sociale, l'ontologie vitale et le vécu subjectif à travers les pensées de Michel Foucault, Georges Canguilhem et Paul-Antoine Miquel. Cette étude nous conduit à envisager une nouvelle politique de la vérité et une compréhension complexe de la maladie humaine.