Environmental changes can disrupt long-standing host-symbiont associations and influence tumor dynamics; however, how these two aspects interact remains poorly understood, particularly when previously co-evolved symbionts are reintroduced into tumor-prone hosts. We experimentally reintroduced a native commensal ciliate symbiont (Kerona pediculus) into two long-term cultured symbiont-free lines of the freshwater cnidarian, Hydra oligactis, differing in tumor affliction: one harbors a transmissible tumor, and one has historically low spontaneous tumor incidence. Unexpectedly, spontaneous tumors emerged at high frequency in the latter, independently of ciliate acquisition, fundamentally reshaping the experimental framework and enabling comparisons of how symbiont reintroduction affects hosts with either transmissible or de novo tumors. While ciliate infection did not alter tumor incidence, it slightly accelerated tumor onset, increased the likelihood of supernumerary tentacle formation, and reduced asexual reproduction (particularly at high symbiont densities) across tumor contexts. Spontaneous tumors appeared later than transmissible tumors, were less often associated with supernumerary tentacles, and induced an earlier reproductive burst. Our findings show that symbiont reintroduction and tumor context shape tumor dynamics and life-history traits in tumor-bearing hosts, emphasizing the potential role of symbiotic history and tumor evolutionary context when assessing the outcomes of such pressures in vulnerable host populations.

Many cancer therapies achieve durable control without complete tumor eradication, suggesting that disrupting tumor organization may be more critical than killing cells. We propose that effective treatments converge by destabilizing the tumor's Group Phenotypic Composition (GPC), the functional and spatial organization of interacting cell populations. When this organization collapses, tumors lose coherence. This perspective provides a unifying framework for designing therapies targeting tumor-level dynamics rather than cell number alone.

Reproduction is a key life-history trait but often comes at the expense of somatic maintenance, including ageing and susceptibility to disease. While reproduction-immunity trade-offs have been experimentally demonstrated in the context of infectious diseases, whether reproduction similarly undermines susceptibility to tumours has remained unclear. Using the freshwater cnidarian Hydra oligactis, in which tumours arise spontaneously and reproductive effort can be experimentally modulated through food availability, we tested the possibility of a trade-off between reproduction and tumour dynamics. Higher reproductive effort increased the likelihood of tumour development, reduced the probability of remission and increased the likelihood of progression to advanced stages. Resource availability modulated the strength of the trade-off in terms of tumour risk and remission, whereas tumour severity was determined solely by reproductive effort. Together, these findings provide rare empirical support for a trade-off between reproduction and tumour dynamics, demonstrating that reproductive investment compromises both tumour prevention and control and that its expression can be shaped by environmental conditions. More broadly, they suggest that cancer susceptibility in more complex lineages may instead reflect evolutionary trade-offs that prioritize reproduction over somatic maintenance, helping illustrate one mechanism by which evolutionary trade-offs contribute to the persistence of cancer and to variation in susceptibility across taxa.

Comparative oncology investigates variation in cancer risk across species by analysing relationships between observed tumour prevalence and factors such as body mass, longevity, life-history traits and mutation rates. These patterns underpin hypotheses on cancer defences, conservation strategies and the evolution of multicellularity, so their robustness is critical. Here, we show that species' scientific and public popularity substantially biases these trends. Reanalysing published captive vertebrate datasets, and re-evaluating previously published trends, we found that controlling for popularity eliminated the weak positive associations previously reported between body mass and both tumour and malignancy prevalence, supporting Peto's paradox. The positive link between germline mutation rate and cancer mortality also disappeared. In birds, the effect of clutch size doubled for species with a large clutch size, while in mammals, tumour prevalence was underestimated in less popular species. Finally, the endotheliochorial placentation-mortality association vanished after accounting for confounders. These findings reveal that species popularity can substantially distort comparative cancer analyses and should be systematically controlled in future studies.

Human activities are changing the natural world at an accelerating pace, and as a consequence exerting novel and often strong selection pressures on living organisms. For species with traits conferring huge inherent evolutionary potential, like parasites, the outcome may be rapid adaptive responses spanning multiple phenotypic traits. The rise of drug resistance in parasites of domesticated animals is well documented; however, rapid changes in other key parasite traits may go unnoticed. In this contribution to the Scientists' Warning series, we argue that parasites are capable of evolving quickly to meet the new pressures of the Anthropocene. After summarizing evidence demonstrating their ability to evolve quickly and the magnitude of the anthropogenic selection pressures they now face, we discuss the basic types of adaptive responses we might expect. Next, we propose methods to track rapid parasite evolution in real time, as well as possible approaches to either slow it down or mitigate its impact on animal production systems. Our aim is to raise awareness of this concerning but underappreciated phenomenon and appeal for greater research into rapid parasite evolution in the Anthropocene and its consequences.

Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be. The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance. Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation. Our results show that the expansion of the MHC class I gene complex, as well as increased selection for diversity at these genes is associated with sharply decreasing cancer mortality risk across mammals. This suggests that the efficient presentation of diverse peptides in somatic cells is important for cancer suppression across mammals, providing pioneering evidence that supports the cancer immunosurveillance hypothesis across species.

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.

Comparative oncology is a rapidly expanding field that seeks to explain variation in cancer risk across species by examining trends between tumour prevalence and key risk factors such as body mass, longevity, life history traits, and mutation rates. These trends are then used to address fundamental questions in the field, including the discovery of potential novel anti-cancer therapies, improvements to species conservation efforts, and understanding how cancer has influenced the evolution of multicellularity. They thus must be robust. This study demonstrates that when estimated on captive species those trends are heavily influenced by their scientific and public popularity, and that accounting for this bias can substantially alter their direction and magnitude. Hence, we reanalysed published captive vertebrate datasets examining the associations between neoplasia, malignancy, and lethal tumour prevalences with body mass, longevity, life history traits, and germinal cells mutation rates. When we included proxies of species popularity in our analyses, the previously reported weak effect of body mass on tumour and malignancy prevalences disappeared entirely. Similarly, the previously reported positive relationship between germline mutation rate and cancer mortality was eliminated after controlling for popularity bias. For life history traits, the effect of clutch size on cancer neoplasia and malignancy prevalences in birds doubled in magnitude, and while the negative trend between gestation length and tumour prevalence in mammals was not greatly affected, our analyses revealed that baseline tumour prevalences were underestimated for popular animals. Finally, the previously observed association between hemochorial placentation and cancer mortality in mammals was eliminated when confounding variables were included. Collectively, these results demonstrate that current comparative analyses based on tumour prevalence in captive animals are heavily influenced by species’ scientific and public popularities. Future studies utilising such datasets should incorporate measures of species popularity as confounding variables to ensure more robust conclusions and misleading research directions. ### Competing Interest Statement The authors have declared no competing interest. The Hoffmann Family ANR EVOSEXCAN, ANR-23-CE13-0007 CNRS (IRP CANECEV)

Laplane et al. recently provided a valuable framework for understanding cancer evolution through multilevel selection (MLS), distinguishing between MLS1, where groups differ in persistence based on the traits of their constituent cells but do not reproduce or evolve group-level adaptations, and MLS2, where groups themselves reproduce and possess emergent fitness distinct from that of individual cells. However, as the authors themselves acknowledge, applying MLS2 to metastasis is challenging for several reasons. We argue that, rather than behaving as isolated evolutionary units, tumor sites function as components of a distributed system. This perspective suggests that metastasis may be better understood through the lens of selection for function, a framework that explains how traits contributing to system-level persistence can be maintained without requiring group-level reproduction. This approach complements MLS theory and helps account for the resilience of the metastatic system as a whole, namely, the persistence and coordination of multiple tumor sites functioning as a collective rather than as isolated tumors, beyond classical Darwinian models. It also aligns with the view that metastasis may reflect the reactivation of ancient cellular programs in a novel, nonreproductive context.

Oncogenic pressures, factors that increase tumor risk, are intensifying with human-driven environmental change, yet their ecological effects remain mainly unquantified. We examined how UVB-induced oncogenic stress affects interactions between two Australian freshwater planaria: the globally invasive predator Girardia tigrina and the native prey Cura pinguis. We hypothesized that DNA damage could either heighten prey vulnerability or impair predator performance. Native planaria showed less UVB-induced DNA damage, likely due to darker pigmentation, while damage in G. tigrina reduced predation rates, suggesting energetic costs of DNA repair. UVB also reduced movement in both species, with partial recovery in the invasive species but prolonged immobility in the native. Additionally, UVB strongly suppressed asexual reproduction in G. tigrina, indicating trade-offs between DNA repair and proliferation. These results reveal that oncogenic stress can reshape species interactions and invasion dynamics, underscoring the need to integrate cancer ecology into conservation and invasion biology.

Offspring sex ratio has been proposed as an indicator of the risk of developing certain cancers in humans, but offspring sex ratio may also be a consequence of the disease. In this study, we investigate this subject using the zebrafish, Danio rerio, as a model system. First, we explore whether inducing skin cancer at an early stage of the host's life (embryonic stage) has the potential to influence sex determination and/or sex-specific mortality. Second, we investigate whether the sex ratio in offspring produced by tumor-bearing adult females differs from that of healthy females. Third, we compare the survival (until sexual maturity) of offspring produced by cancerous and non-cancerous females. We found that skin cancer did not influence sex determination and the sex ratio of the offspring. However, consistent with previous studies on other model systems, the survival of offspring was higher when mothers were cancerous, suggesting that diseased females allocate more resources to current reproductive effort compared to their healthy counterparts. This study makes a significant contribution to our understanding of the ecological and evolutionary consequences of host-tumor interactions in animals.

Transmissible tumors are increasingly regarded as a new form of parasitic life, but relatively little is known about the ecology and evolution of their interactions with their host. In this work, we provide new insights into transmission dynamics of vertically transmitted tumors in the freshwater cnidarian Hydra oligactis. First, we found tumoral hydra to be infectious at any age, regardless of whether they were in their asymptomatic or symptomatic phases, with the bacteriome composition remaining constant during both phases. Interestingly, tumor transmission increased with the number of tentacles, particularly for hydras with supernumerary tentacles. Additionally, tumors developed earlier in the offspring from parents with more advanced tumors. Furthermore, despite being direct descendants of tumoral polyps, some hydras never developed tumoral phenotype. The latter exhibited a distinct bacteriome composition, reduced lifespan and a lower tentacle number increase over time. Interestingly, the tumor phenotype expression in these hydras appears to be able to skip generations, as transmission occurred at any age from parents to offspring. We discuss these results in the context of current knowledge on the evolutionary ecology of host-transmissible tumor interactions as well as parasite-host interactions and suggest avenues for further research.

While it is often assumed that oncogenic process in metazoans can influence biotic interactions, empirical evidence for that is lacking. Here, we use the cnidarian Hydra oligactis to experimentally explore the consequences of tumor associated phenotypic alterations for the hydra’s predation efficiency, the relationship with commensal ciliates and the vulnerability to predators. Unexpectedly, the efficiency of hydra predation on prey was higher in tumorous polyps compared to non-tumorous ones. Commensal ciliates colonized preferentially tumorous hydras than non-tumorous ones, and had a higher replication rate on the former. Finally, in a choice experiment, tumorous hydras were preferentially eaten by a fish predator. This study, for the first time, provides evidence that neoplastic growth has the potential, through effect(s) on host phenotype, to alter biotic interactions within ecosystems and should thus be necessarily taken into account by ecologists.

IntroductionToxoplasma gondii (TG) is a common protozoan parasite infecting approximately one third of the human population. Animal studies have shown that this parasite can manipulate its host behavior. Based on this, human studies have assessed if TG can be involved in mental health disorders associated with important behavioral modifications such as schizophrenia. However, results have been discrepant. Given that TG has a strong impact on fear and risk-taking processes in animal studies and that fear and risk-taking behaviors are associated with the human stress response, we tested whether glucocorticoid biomarkers (salivary and hair) differ in people with schizophrenia and controls as a function of TG status. MethodsWe measured TG antibodies in blood samples, as well as salivary and hair glucocorticoid levels in 226 people with schizophrenia (19.9% women, mean age = 39 years old) and 129 healthy individuals (controls) (45.7% women, mean age = 41 years old). ResultsThe results showed that people with schizophrenia infected with TG presented significantly higher hair glucocorticoid concentrations than non-infected people with schizophrenia. This effect was not found in control participants. No effect was observed for salivary glucocorticoid levels. Additionally, there were no associations between TG infection and positive psychotic symptoms nor impulsivity. DiscussionThese results show that people with schizophrenia present high levels of hair glucocorticoid levels only when they are infected with TG. Further studies performed in populations suffering from other mental health disorders are needed to determine if this effect is specific to schizophrenia, or whether it is generalized across mental health disorders.

AbstractWhile 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 cnidarianHydra 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.

Tumorigenesis is commonly attributed to Darwinian processes involving natural selection among cells and groups of cells. However, progressing tumors are those that also achieve an appropriate group phenotypic composition (GPC). Yet, the selective processes acting on tumor GPCs are distinct from that associated with classical Darwinian evolution (i.e. natural selection based on differential reproductive success) as tumors are not genuine evolutionary individuals and do not exhibit heritable variation in fitness. This complex evolutionary scenario is analogous to the recently proposed concept of 'selection for function' invoked for the evolution of both living and non-living systems. Therefore, we argue that it is inaccurate to assert that Darwinian processes alone account for all the aspects characterizing tumorigenesis and cancer progression; rather, by producing the genetic and phenotypic diversity required for creating novel GPCs, these processes fuel the evolutionary success of tumors that is dependent on selection for function at the tumor level.

Growing evidence indicates that human activities are causing cancer rates to rise in both human and wildlife populations. This is due to the inability of ancestral anti-cancer defences to cope with modern environmental risks. The evolutionary mismatch between modern oncogenic risks and evolved cancer defences has far-reaching effects on various biological aspects at different timeframes, demanding a comprehensive study of the biology and evolutionary ecology of the affected species. Firstly, the increased activation of anti-cancer defences leads to excessive energy expenditure, affecting other biological functions and potentially causing health issues like autoimmune diseases. Secondly, tumorigenesis itself can impact important fitness-related parameters such as competitiveness, predator evasion, resistance to parasites, and dispersal capacity. Thirdly, rising cancer risks can influence the species' life-history traits, often favoring early reproduction to offset fitness costs associated with cancer. However, this strategy has its limits, and it may not ensure the sustainability of the species if cancer risks continue to rise. Lastly, some species may evolve additional anti-cancer defences, with uncertain consequences for their biology and future evolutionary path. In summary, we argue that the effects of increased exposure to cancer-causing substances on wildlife are complex, ranging from immediate responses to long-term evolutionary changes. Understanding these processes, especially in the context of conservation biology, is urgently needed.

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.

Cancer is an inevitable collateral problem inherent in the evolution of multicellular organisms, which appeared at the end of the Precambrian. Faced to this constraint, a range of diverse anticancer defenses has evolved across the animal kingdom. Today, investigating how animal organisms, especially those of large size and long lifespan, manage cancer-related issues has both fundamental and applied outcomes, as it could inspire strategies for preventing or treating human cancers. In this article, we begin by presenting the conceptual framework for understanding evolutionary theories regarding the development of anti-cancer defenses. We then present a number of examples that have been extensively studied in recent years, including naked mole rats, elephants, whales, placozoa, xenarthras (such as sloths, armadillos and anteaters) and bats. The contributions of comparative genomics to understanding evolutionary convergences are also discussed. Finally, we emphasize that natural selection has also favored anti-cancer adaptations aimed at avoiding mutagenic environments, for example by maximizing immediate reproductive efforts in the event of cancer. Exploring these adaptive solutions holds promise for identifying novel approaches to improve human health.