Ultrastuctural study of the phagocytic activities of splenic macrophages in tilapia (Oreochromis niloticus)

The main stages of the phagocytic process after the intraperitoneal injection of colloidal carbon to tilapia (Oreochromis niloticus), was ultra-structurally documented. Carbon particles were initially indiffuse form in the cytoplasm but they gradually formed discrete electron dense bodies that later fused with cytoplasmic granules to form phagolysosomes. Ultra structural results demonstrate that colloidalcarbon is actively phagocytized by cytoplasmic granules (lysosomes) in the spleen of O. niloticus. Direct phagocytic reaction of cells in the presence of an antigen is therefore very important in immunity

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Organ-on-chip models of cancer metastasis for future personalized medicine: from chip to the patient

Most cancer patients do not die from the primary tumor but from its metastasis. Current in vitro and in vivo cancer models are incapable of satisfactorily predicting the outcome of various clinical treatments on patients. This is seen as a serious limitation and efforts are underway to develop a new generation of highly predictive cancer models with advanced capabilities. In this regard, organ-on-chip models of cancer metastasis emerge as powerful predictors of disease progression. They offer physiological-like conditions where the (hypothesized) mechanistic determinants of the disease can be assessed with ease. Combined with high-throughput characteristics, the employment of organ-on-chip technology would allow pharmaceutical companies and clinicians to test new therapeutic compounds and therapies. This will permit the screening of a large battery of new drugs in a fast and economic manner, to accelerate the diagnosis of the disease in the near future, and to test personalized treatments using cells from patients. In this review, we describe the latest advances in the field of organ-on-chip models of cancer metastasis and their integration with advanced imaging, screening and biosensing technologies for future precision medicine applications. We focus on their clinical applicability and market opportunities to drive us forward to the next generation of tumor models for improved cancer patient theranostics.- The authors acknowledge the financial support from the European Union Framework Programme for Research and Innovation Horizon 2020 on Forefront Research in 3D Disease Cancer Models as in vitro Screening Technologies (FoReCaST) under grant agreement no 668983. Conflicts of interest: none.info:eu-repo/semantics/publishedVersio