Abstract While most cancers are not transmissible, there are rare cases where cancer cells have acquired the ability to spread vertically or horizontally to other individuals, and sometimes species, causing epidemics in their hosts. However, as these transmissible cancers are usually detected once they are relatively well disseminated in host populations, the conditions associated with their origin remain poorly understood. Using the freshwater cnidarian Hydra oligactis , which exhibits spontaneous tumor development that in some strains became vertically transmitted, this study presents the first experimental observation of the evolution of a transmissible tumor. Specifically, we assessed the initial vertical transmission rate of spontaneous tumors and explored the potential for optimizing this rate through artificial selection. One of the hydra strains, which evolved transmissible tumors over five generations, was characterized by analysis of cell type and microbiome, as well as assessment of life-history traits. Our findings indicate that tumor transmission can be immediate for some strains and can be enhanced by selection. The resulting tumors are characterized by overproliferation of large interstitial stem cells and, in contrast with other transmissible tumors on Hydra, are not associated with a specific microbiome. Furthermore, although tumor transmission has only been established over 5 generations, it was sufficient to alter life-history traits in the host, suggesting a compensatory response. This work, therefore, makes the first contribution to understanding the conditions of transmissible cancer emergence and their short-term consequences for the host.
Abstract While host phenotypic manipulation by parasites is a widespread phenomenon, whether tumors – which can be likened to parasite entities, can also manipulate their hosts is not known. Theory predicts that this should nevertheless be the case, especially when tumors (neoplasms) are transmissible. We explored this hypothesis in a cnidarian Hydra model system, in which spontaneous tumors can occur in the lab, and lineages in which such neoplastic cells are vertically transmitted (through host budding) have been maintained for over 15 years. Remarkably, the hydras with long-term transmissible tumors show an unexpected increase in the number of their tentacles, allowing for the possibility that these neoplastic cells can manipulate the host. By experimentally transplanting healthy as well as neoplastic tissues derived from both recent and long-term transmissible tumors, we found that only the long-term transmissible tumors were able to trigger the growth of additional tentacles. Also, supernumerary tentacles, by permitting higher foraging efficiency for the host, were associated with an increased budding rate, thereby favoring the vertical transmission of tumors. To our knowledge, this is the first evidence that, like true parasites, transmissible tumors can evolve strategies to manipulate the phenotype of their host.
While most cancers are not transmissible, there are rare cases where cancer cells can spread between individuals and even across species, leading to epidemics. Despite their significance, the origins of such cancers remain elusive due to late detection in host populations. Using Hydra oligactis , which exhibits spontaneous tumour development that in some strains became vertically transmitted, this study presents the first experimental observation of the evolution of a transmissible tumour. Specifically, we assessed the initial vertical transmission rate of spontaneous tumours and explored the potential for optimizing this rate through artificial selection. One of the hydra strains, which evolved transmissible tumours over five generations, was characterized by analysis of cell type and bacteriome, and assessment of life-history traits. Our findings indicate that tumour transmission can be immediate for some strains and can be enhanced by selection. The resulting tumours are characterized by overproliferation of large interstitial stem cells and are not associated with a specific bacteriome. Furthermore, despite only five generations of transmission, these tumours induced notable alterations in host life-history traits, hinting at a compensatory response. This work, therefore, makes the first contribution to understanding the conditions of transmissible cancer emergence and their short-term consequences for the host.
Recent theoretical advances in the One Health approach propose that greater attention should be paid to cancer pathologies due to their potential to render hosts more susceptible to infectious agents, potentially transforming them into super-spreaders within ecosystems. However, this hypothesis lacks experimental validation. Using a community of Hydra species and a commensal ciliate species (Kerona pediculus) that colonizes them, we tested whether tumoral polyps of H. oligactis, compared to healthy ones, played an amplifying role in ciliate load, potentially resulting in higher likelihood of infection for other community members through spillovers. Results revealed a higher proliferation rate of ciliates on tumoral polyps compared to healthy ones, leading to infection of other hydras, albeit with varying spillover magnitudes among recipient species. This study is the first proof of concept that tumoral individuals within communities could act as super-spreaders of symbionts within and between species, influencing biotic interactions and dynamics in ecosystems.
IMMUcan (SPECTA NCT02834884) is a European initiative to profile the tumor microenvironment (TME) for a better understanding of immune-tumor interactions. Here, we explored the association between distinct molecular phenotypes and spatial TME patterns in the prospective neoadjuvant IMMUcan TNBC cohort. From a preliminary cohort of 132 patients, matched baseline RNA-seq and multiplex immune fluorescence (mIF) data were available for 66 cases. The mIF panel included CD8, PD1, PD-L1, granzyme B (GB), Ki67 and CK markers. Spatial TME patterns were defined by a graph-based approach detecting densely populated regions of tumor cells and their immune neighbors. TNBC molecular subtypes were derived from RNA-seq as described by Bareche et al. Area Under the Curve (AUC) was used to evaluate the accuracy of spatial patterns to predict TNBC subtypes. A total of eight distinct clusters were identified across the 66 samples, each exhibiting a specific spatial distribution of mIF markers. Two of the clusters showed high performance in predicting immunomodulatory phenotype (AUC: 0.72, 0.71, respectively). These clusters presented elevated densities of CD8+, CD8+/GB+, and CD8+/Ki67+ cells, consistent with CD8+ effector T cells. In addition, a cluster characterized by tumor cells correlated with the luminal androgen-receptor phenotype (AUC: 0.91). The basal-like phenotype was represented by a cluster exhibiting high levels of Ki67+ tumor cells (AUC: 0.61). A distinct cluster displaying an intermediate proportion of Ki67+ tumor cells was observed as well, representing the mesenchymal subtype (AUC: 0.69). These preliminary analyses revealed the presence of informative spatial patterns populating mIF data, linked to the distribution of immune/tumor markers within the TME of TNBC. Of note, these spatial patterns were associated with distinct RNA-seq TNBC subtypes. These findings suggest the predictive power of mIF markers as a potential surrogate to discern TNBC heterogeneity. Consequently, these observations, if confirmed by further validations, could facilitate the implementation of treatment strategies tailored to the TNBC molecular subtypes.
Recent theoretical advances in the One Health approach have suggested that cancer pathologies should be given greater consideration, as cancers often render their hosts more vulnerable to infectious agents, which could turn them into super spreaders within ecosystems. Although biologically plausible, this hypothesis has not yet been validated experimentally. Using a community of cnidarians of the Hydra genus (Hydra oligactis, Hydra viridissima, Hydra vulgaris) and a commensal ciliate species (Kerona pediculus) that colonizes them, we tested whether tumoral polyps of H. oligactis, compared to healthy ones, played an amplifying role in the number of ciliates, potentially resulting in a higher likelihood of infection for other community members through spillovers. Our results indicate that K. pediculus has a higher proliferation rate on tumoral polyps of H. oligactis than on healthy ones, which results in the infestation of other hydras. However, the magnitude of the spillover differed between recipient species. This study provides to our knowledge the first elements of proof of concept that tumoral individuals in communities could act as super spreaders of symbionts within and between species, and thus affect biotic interactions and dynamics in ecosystems.
Be it to aerate a glass of wine before tasting, to accelerate a chemical reaction or to cultivate cells in suspension, the "swirling" (or orbital shaking) of a container ensures good mixing and gas exchange in an efficient and simple way. Despite being used in a large range of applications this intuitive motion is far from being understood and presents a richness of patterns and behaviors which has not yet been reported. The present research charts the evolution of the waves with the operating parameters identifying a large variety of patterns, ranging from single and multiple crested waves to breaking waves. Free surface and velocity fields measurements are compared to a potential sloshing model, highlighting the existence of various flow regimes. Our research assesses the importance of the modal response of the shaken liquids, laying the foundations for a rigorous mixing optimization of the orbital agitation in its applications. Copyright (2014) American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Physics of Fluids 26, 052104 (2014) and may be found at http://dx.doi.org/10.1063/1.4874612
Tumoural processes, ubiquitous phenomena in multicellular organisms, influence evolutionary trajectories of all species. To gain a holistic understanding of their impact on species' biology, suitable laboratory models are required. Such models are characterised by a widespread availability, ease of cultivation, and reproducible tumour induction. It is especially important to explore, through experimental approaches, how tumoural processes alter ecosystem functioning. The cnidarian Hydra oligactis is currently emerging as a promising model due to its development of both transmissible and non-transmissible tumours and the wide breadth of experiments that can be conducted with this species (at the individual, population, mechanistic, and evolutionary levels). However, tumoural hydras are, so far, only documented in Europe, and it is not clear if the phenomenon is local or widespread. In this study we demonstrate that Australian hydras from two independent river networks develop tumours in the laboratory consisting of interstitial stem cells and display phenotypic alterations (supernumerary tentacles) akin to European counterparts. This finding confirms the value of this model for ecological and evolutionary research on host-tumour interactions. • Tumoral processes are important to understanding evolutionary biology and ecosystem dynamics • There is a need for good laboratory models in a context of increased oncogenic pressures • We show that Hydra oligactis has widespread geographical vulnerabilities to tumorigenesis • This species is thus a great model to study the effect of tumours on ecosystem functioning • We discuss the implications of using this model in future comparative studies
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