Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer.
A severe epidemic of rinderpest, affecting mainly wild ruminants, occurred between 1993 and 1997 in East Africa. Buffalo (Syncerus caffer), eland (Taurotragus oryx) and lesser kudu (Tragelaphus imberbis) were highly susceptible. The histopathological changes, notably individual epithelial cell necrosis with syncytia formation, were consistent with an infection with an epitheliotrophic virus. Serology, the polymerase chain reaction, and virus isolation confirmed the diagnosis and provided epidemiological information. The virus was related to a strain which was prevalent in Kenya in the 1960s, of a second lineage (II), and distinct from isolations of rinderpest virus in the region since 1986. The source of the virus was presumed to be infected cattle from the Eastern region of Kenya and Somalia. The pathogenicity of the virus varied during the epidemic. The mortality in buffalo populations was estimated to be up to 80 per cent, and population data suggested that the virus had an adverse effect on a wide range of species. The virus caused only a mild disease in cattle, with minimal mortality. The results confirmed the importance of wildlife as sentinels of the disease, but although wildlife were important in the spread of the virus, they did not appear to act as reservoirs of infection.
Comparative studies were made to determine the most suitable microtitration system for assaying strains of peste des petits ruminants virus (PPRV) and rinderpest virus (RV). Infectivity titres did not differ significantly when assayed in either calf kidney, sheep kidney or Vero cells. However, cytopathic effects were much easier to detect in the latter making them the cell of choice. Addition of small amounts of virus to preformed cell monolayers in microplates with the subsequent addition of maintenance medium give higher infectivity titres than when cell suspension was added to virus, although the latter is more convenient for routine use. The titres of PPRV and neutralising antibodies assayed in tubes and microplates were not significantly different. Simultaneous screening of sera at a 1 in 20 dilution against both PPRV and RV gave a higher incidence of positives against homologous as opposed to heterologous virus.
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