RESUMO
Cellular immunotherapy has revolutionized the oncology field, yielding improved results against hematological and solid malignancies. NK cells have become an attractive alternative due to their capacity to activate upon recognition of "stress" or "danger" signals independently of Major Histocompatibility Complex (MHC) engagement, thus making tumor cells a perfect target for NK cell-mediated cancer immunotherapy even as an allogeneic solution. While this allogeneic use is currently favored, the existence of a characterized memory function for NK cells ("memory-like" NK cells) advocates for an autologous approach, that would benefit from the allogeneic setting discoveries, but with added persistence and specificity. Still, both approaches struggle to exert a sustained and high anticancer effect in-vivo due to the immunosuppressive tumor micro-environment and the logistical challenges of cGMP production or clinical deployment. Novel approaches focused on the quality enhancement and the consistent large-scale production of highly activated therapeutic memory-like NK cells have yielded encouraging but still unconclusive results. This review provides an overview of NK biology as it relates to cancer immunotherapy and the challenge presented by solid tumors for therapeutic NKs. After contrasting the autologous and allogeneic NK approaches for solid cancer immunotherapy, this work will present the current scientific focus for the production of highly persistent and cytotoxic memory-like NK cells as well as the current issues with production methods as they apply to stress-sensitive immune cells. In conclusion, autologous NK cells for cancer immunotherapy appears to be a prime alternative for front line therapeutics but to be successful, it will be critical to establish comprehensives infrastructures allowing the production of extremely potent NK cells while constraining costs of production.
Assuntos
Imunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Células Matadoras Naturais , Microambiente TumoralRESUMO
The delimitation of cryptic species within the genus Lymnaea, which are the main vectors of fascioliasis, remains a topic of controversy. An analysis of genetic variability based on 12 enzyme loci revealed different fixed alleles at 9 loci between two sympatric samples of Lymnaea viatrix at the type locality in Lima, Peru. The absence of heterozygotes within this locality indicates the presence of isolated populations or cryptic species within L. viatrix. Significant genetic differences were also found between these two L. viatrix samples from Lima and other populations of L. viatrix in South America and in addition to species such as L. truncatula, L. cubensis and L. columella. Moreover, the lack of variability within each Lymnaea samples studied indicates the existence of a high selfing rate in each species.
Assuntos
Lymnaea/genética , Animais , Vetores de Doenças , Fasciolíase/transmissão , Genótipo , América do Sul , Especificidade da EspécieRESUMO
Fasciolosis is a re-emerging parasitic disease that affects an increasing number of people in developing countries. The most severe endemic affects the Bolivian Altiplano, where the liver fluke (Fasciola hepatica) and its hermaphroditic snail host, Lymnaea truncatula, have been introduced from Europe. To achieve a better understanding of the epidemiological situation and the consequences of the colonization event of this invasive species, genetic analysis of Bolivian snail populations was needed. Here we compare the genetic diversity and population structure of snail samples from the Bolivian Altiplano with samples from the Old World at six polymorphic microsatellite loci. Whereas some variability exists in the snail populations from the Old World, we observe only a single genotype of L. truncatula in the Bolivian Altiplano. We discuss the possible explanations for such a reduction in genetic variability, and, given the high natural parasitism pressures exerted on the snail populations, we discuss the relevance of this result for host-parasite interactions.
Assuntos
Genética Populacional , Caramujos/genética , Caramujos/parasitologia , Animais , Bolívia , Europa (Continente) , Interações Hospedeiro-Parasita , Repetições de MicrossatélitesRESUMO
Los autores presentaron los resultados obtenidos del estudio de 43 muestras recogidas en 25 lugares de cinco estados de Venezuela. Las muestras fueron cultivadas para aislamiento de nocardia sp. usando la técnica del "paraffin bait". Las muestras de suelo fueron recolectadas en el estado Lara (19 muestras), estado Mérida (13 muestras), estado Amazonas (7 muestras), estado Falcón (3 muestras) y estado Apure (1 muestra). De las muestras estudiadas, el 46,51 por ciento se identificaron como nocardia asteroides y el el 16,28 por ciento como nocardias sp. En las muestras de suelo estudiadas del estado Lara se encontró el mayor número de aislados de nocardia asteroides (95 por ciento); esto es un indicador de que este estado podría ser considerado como uno de los reservarios naturales de N. asteroides. Estos datos se compaginan con la alta morbilidad del actinomicetoma, entre los cuales figura como segundo agente etiológico del mismo N. asteroides
Assuntos
Classificação , Ecologia , Nocardia asteroides , Separação Celular , Microbiologia , VenezuelaRESUMO
A population genetic study using starch gel electrophoresis was performed on populations of several species of lymnaeid snails acting as intermediate hosts for Fasciola hepatica (Trematoda, Plathyhelminth). Lymnaea viatrix was collected in 16 sites from the Bolivian Northern Altiplano. L. cubensis were obtained in one site from Venezuela, one site from Guadeloupe, three sites from Cuba and one site from the Dominican Republic. L. truncatula were collected in one site from France, one from Portugal and one from Morocco. Multilocus enzyme electrophoresis (MEE) were determined for 282 snails at 18 loci. A complete monomorphism was encountered at each geographic site. However, among these 18 loci, 13 are polymorphic and low and high levels of genetic divergence were observed between samples. Two genotypic groups can be differentiated by their multilocus genotypes. The western genotypic group associates together samples from Venezuela, Guadeloupe, Cuba and Dominican Republic (L. cubensis) while samples from France, Portugal and Morocco (L. truncatula) belong to the eastern genotypic group. Surprisingly, the Northern Bolivian Altiplano populations (L. viatrix) do not present any genetic divergence with the Portuguese sample. Therefore, the Bolivian snails belong entirely to the eastern genetic group. Within each group slight genetic divergences were observed. These results strongly support the European origin of the lymnaeid snails from the Northern Bolivian Altiplano.
Assuntos
Reservatórios de Doenças/classificação , Genética Populacional , Lymnaea/classificação , Lymnaea/genética , Animais , Bolívia , Cuba , República Dominicana , Eletroforese em Gel de Poliacrilamida , Fasciolíase/epidemiologia , França , Guadalupe , Humanos , Lymnaea/parasitologia , Marrocos , Filogenia , Polimorfismo Genético , Portugal , VenezuelaRESUMO
Allelic frequency variation at the malate dehydrogenase (E.C.1.1.1.37) polymorphic locus (Mdh-1) was analysed during several successive generations in four strains of Schistosoma mansoni from Guadeloupe, maintained experimentally on mice. A rapid evolution of the frequency of the Mdh-1a allele is interpreted as being the result of an interaction between experimental drift and selection induced by the murine laboratory host. These experimental results are compared to the genetic structures observed among the corresponding natural populations of S. mansoni in Guadeloupe (West Indies). They strengthen the hypothesis of a natural host-induced selection by the murine host (Rattus rattus), which, in Guadeloupe, plays the role of host reservoir for this human schistosome.