Quantitative and qualitative impairments in dendritic cell subsets of patients with ovarian or prostate cancer

Background Dendritic cells (DCs) are the most efficient antigen-presenting cells, hence initiating a potent and cancer-specific immune response. This ability (mainly using monocyte-derived DCs) has been exploited in vaccination strategies for decades with limited clinical efficacy. Another alternative would be the use of conventional DCs (cDCs) of which at least three subsets circulate in human blood: cDC1s (CD141bright), cDC2s (CD1c+) and plasmacytoid DCs. Despite their paucity, technical advances may allow for their selection and clinical use. However, many assumptions concerning the DC subset biology depend on observations from mouse models, hindering their translational potential. In this study, we characterise human DCs in patients with ovarian cancer (OvC) or prostate cancer (PrC). Patients and methods Whole blood samples from patients with OvC or PrC and healthy donors (HDs) were evaluated by flow cytometry for the phenotypic and functional characterisation of DC subsets. Results In both patient groups, the frequency of total CD141+ DCs was lower than that in HDs, but the cDC1 subset was only reduced in patients with OvC. CD141+ DCs showed a reduced response to the TLR3 agonist poly (I:C) in both groups of patients. An inverse correlation between the frequency of cDC1s and CA125, the OvC tumour burden marker, was observed. Consistently, high expression of CLEC9A in OvC tissue (The Cancer Genome Atlas data set) indicated a better overall survival. Conclusions cDC1s are reduced in patients with OvC, and CD141+ DCs are quantitatively and qualitatively impaired in patients with OvC or PrC. CD141+ DC activation may predict functional impairment. The loss of cDC1s may be a bad prognostic factor for patients with OvC

Interacción tripanosoma-vector-vertebrado y su relación con la sistemática y la epidemiología de la tripanosomiasis americana

Introduction. Trypanosoma rangeli is a species of trypanosome second to T. cruzi, that is infective to humans in Latin America. Variability in the biological, biochemical and molecular characteristics between different isolates isolates of this parasite have been recorded.Objective. Morphological and molecular characteristics were recorded from strains of T. rangeli that were isolated from different species of Rhodnius and maintained in different vertebrate species.Materials and methods. Nineteen strains of T. rangeli were isolated from R. prolixus, R. pallescens and R. colombiensis in Colombia, R. ecuadoriensis in Peru and R. pallescens in Panama. Polymorphism of blood trypomastigotes in ICR mice was evaluated and pleomorphism of P53 strain of T. rangeli KP1(-) inoculated in mouse, marsupial and canine was studied. RAPD analysis (randomly amplified polymorphic DNA analysis) of 12 strains isolated from four species of Rhodnius was performed.Result. Based on the total length of blood trypomastigotes, three discrete groups were observed. The P53 strain showed significant differences in the size of blood trypomastigotes in mouse, marsupial and canine. RAPD analysis showed that the strains segregated into two branches corresponding to strains of T. rangeli KP1(+) and T. rangeli KP1(-). All strains of T. rangeli KP1 (-) clustered according to the species of Rhodnius from which they were isolated .Conclusion. These data reveal, for the first time, a close association amongst T. rangeli strains and Rhodnius species, confirming that each species of Rhodnius transmits to vertebrate hosts a parasite population with clear phenotypic and genotypic differences. This is further evidence that supports the concept of clonal evolution of these parasites.Introducción. Trypanosoma rangeli es la segunda especie de tripanosoma que infecta al hombre en América Latina. Se ha observado variabilidad en las características biológicas, bioquímicas y moleculares en diferentes aislamientos de este parásito.Objetivo. Estudiar las características morfológicas y moleculares de cepas de T. rangeli aisladas de diferentes especies de Rhodnius e inoculadas en diferentes especies de vertebrados. Materiales y métodos. Se utilizaron 19 cepas de T. rangeli aisladas de R. prolixus, R. pallescens y R. colombiensis en Colombia, R. ecuadoriensis en Perú y R. pallescens en Panamá. Se evaluó el polimorfismo de los tripomastigotes sanguíneos en ratones ICR y se estudió el pleomorfismo de la cepa P53 de T. rangeli KP1(-) inoculada en ratón, marsupial y canino. Se efectuó análisis de ADN polimorfo amplificado aleatorio en 12 cepas aisladas de cuatro especies de Rhodnius.Resultados. Se observaron tres grupos discretos en la longitud total de los tripomastigotes sanguíneos y la cepa P53 presentó diferencias significativas en el tamaño de los tripomastigotes sanguíneos en ratón, marsupial y canino. El análisis de ADN polimorfo amplificado aleatorio mostró segregación de las cepas en dos ramas correspondientes a las cepas de T. rangeli KP1(+) y T. rangeli KP1(-). De otra parte todos las cepas de T. rangeli KP1(-) se agruparon de acuerdo con las especies de Rhodnius de las cuales fueron aisladas.Conclusión. Este es el primer estudio que revela una estrecha asociación entre cepas de T. rangeli y las especies de Rhodnius, confirmando que cada especie de Rhodnius transmite al hospedero vertebrado poblaciones del parásito con claras diferencias fenotípicas y genotípicas, lo cual soporta la evolución clonal de estas poblaciones

Caracterización genética de poblaciones de Trypanosoma rangeli aisladas en ciclos de transmisión silvestre y doméstica en Colombia :

IP 1115-04-018-99Epidemiologia molecular de trypanosoma rangeli en Colombiay enAmerica /Gustavo Adolfo Vallejo, Julio Cesar;Carranza, Felipe Guhl. -- En: Entornos. -- No.13(jun. 2001); p.10-15. --ISSN01247905. -- Characterization of;two disticn strain groups of trypanosoma rangeli circulating indomestic and silvatic cycles in Colombia /;Gustavo A. Vallejo, Julio C. Carranza, Leyder E. Lozano, JorgeL. Sanchez,Jose C. Jaramillo, Diego Gualtero,;Felipe Guhl. -- En: Memorias do Isntituto Oswaldo Cruz. --Vol.95, suplemento II (2000); p. 42-45. --;ISSN16788060. -- PONENCIA(S) EN CONGRESO: Epidemiolgia detrypanosoma rangeli dos grupos de cepas moleculares;ARTICULO(S) EN REVISTA : Interruption of chagas disease transmission in the countries: Colombia / Felipe;distintas con circulacion independiente en ciclos domesticos ysilvestresen Colombia / Gustavo A. Vallejo,;Julio C. Carranza, Leyder E. Lozano, Jorge L. Sanchez, Jose C.Jaramillo,Diego Gualtero, Felipe Guhl. -- En:;Congreso Latinoamericano de Parasitologia (14:1999 oct. 11-16Acapulco Guerrero, Mexico). -- Caracterizacion;molecular de trypanosoma rangeli t. cruzi en vectores domiciliados y no domiciliados en Colombia / Gustavo A.;Vallejo, Julio C. Carranza, Leyder E. Lozano, Jorge L. Sanchez,Jose C. Jaramillo, Diego Gualtero, Felipe;Guhl. En: Congreso Latinoamericano de Parasitologia (14:1999 oct. 11-16 Acapulco Guerrero, Mexico). --;Demostracion por metodos debiologia molecular de una infeccionmixta de trypanosoma cruzi t. rangeli aislada;por hemocultivo de un paciente de Santander Colombia / GustavoA. Vallejo,Julio C. Carranza, Leyder E.;Lozano, Jorge L. Sanchez, Jose C. Jaramillo, Diego Gualtero, Felipe Guhl.En: Congreso Latinoamericano de;Parasitologia (14:1999 oct. 11-16 Acapulco Guerrero, Mexico).--Biological and molecular charcterization of;trypanosoma rangeli strains / E C. Grisard, L B. Koerich,C. Quimelli, R G. Patzlaff, J H. de Almeida, G A.;Vallejo. En: The tenth International Congress of Parasitology(10: 2002 agus. 4-9 :Vancuver, Canada). --;Caracterizacion biologica y molecular de cepas de trypanosomarangeli aisladas de rhodnius prolixus rhodnius;colombiensis / Gustavo A. Vallejo, Julio C. Carranza, Leyder E.Lozano, Jorge L. Sanchez, Jose C. Jaramillo,;Diego Gualtero, Felipe Guhl. -- Congreso de InvestigacinesenParasitologia Tropical (2000 may.22- jun.2 :;Ibague, Colombia). -- Afinidad por lectinas sencibilidad alaslisis mediada por el complemento y produccion;Guhl, Gustavo A. Vallejo. -- En. Memorias do Instituto OswaldoCruz. -- Vol. 94 suplemento 1 (1999); p.;413-415. -- ISSN16788060. -- Amplification of specific repetitive DNA sequence for trypanosoma rangel;identification and its potential application in epidemilogical/Nancy Vargas, Ricardo P. Souto, Julio C.;de neuraminidasa en cepas domesticas y silvestres de trypanosomarangeli aisladas en Colombia / Bernal M.,;Vallejo. G, Guhl, Felipe, Cornelis J M. En: Congreso NacionaldeCienciasBiologicas (34: 2001otc. 10-13 :Cart;Colombia). -- Caracterizacion molecularde KNDA y del espaciadoeno transcrito del gen mini-exon en cepas de;trypanosoma rangeli aisladas de rhodnius ecuadoriensis enel norte de Peru/ Gustavo A. Vallejo, Julio C.;Carranza.;Carranza, Gustavo A. Vallejo, Blanca Zingales. -- En: Experimental Parasitology. -- Vol. 96. (2000); p. 147-15;ISSN00144894. -- KDNA maekers define two major Trypanosomarangeli lineages in Latin America / Gustavo A.;Vallejo, Felipe Guhl, Julio C. Carranza, Leyder E. Lozano,JorgeL. Sanchez, Jose C. Jaramillo, Diego;Gualtero, Nadia Castañeda, Julio C. Silva, Mario Steidel.'-- en:Acta Tropica. -- Vol. 81, (2002); p. 77-82.;'-- ISSN01247905. -- Molecular characterizacion and diagnosis ofTrypanosoma cruzi and T. rangel / Felipe Guhl,;Carlos Jaramillo, Julio C. Carranza, Gustavo A. Vallejo. -'- en:Archives of Medical Research. -- Vol.;33,(2002); p. 362-370. -- ISSN16788060. -- La Biologia moleculary sus aplacaciones en el estudio de la;tripanosomiasis americana / Gustavo Adolfo Vllejo, Jose CesarJaramillo, Julio Cesar Crranza, Jorge Lorenzo;Sanchez, Leyder Elena Lozano, Diego Gualtero, Froylan Guayara,Ludwin Andres Cuervo, Maria Teresa Mojica,;Carlos Alberto Jaramillo, Felipe Guhl. -- En: Medicina. --Vol.22 no. 2 (agos. 2002); p. 105-112. -

Caracterización antigénica de poblaciones de trypanosoma rangeliaisladasen ciclos de transmisión doméstica y silvestre en Colombia :

IP 1105-05-279-99Guhl. -- En: Mem inst Oswaldo Cruz. -- Vol. 96, no. 8 (nov. 201); p. 1043-1048. -- Molecular characterization;and diagnosis of trypanosoma cruzi and T. rangeli / FelipeGuhl,Carlos Jaramillo, Julio Cesar Carranza,;Gustavo Adolfo Vallejo. -- En: Archives of medical research. --No. 33 (2002); p. 362-370. -- kDNA markers;define two major trypanosoma rangeli lineages in latin America/Gustavo Adolfo Vallejo, Felipe Guhl, Julio;Cesar Carranza, Leyder Elena Lozano, Jorge L. Sanchez, Jose C.Jaramillo,Diego Gualtero, Nadia Castañeda,;Julio C. Silva, Mario Steindel. -- En: Acta tropica. -- No. 81(2002); p.77-82. -- Short technical reports:;Hybridization screening of very short PCR products for paleoepidemiological studies of chagas disease. -- En:;Biotechniques. -- No. 30 (Jan. 2001); p. 102-109. -- Parity betwen kinetoplast DNA and mini exon gene;sequences supports either clonal evolution or speciation in trypanosoma rangeli strains isolated from rhodnius;colombiensis, R. pallescens and R. prolixus in Colombia /Gustavo adolfo Vallejo, Felipe Guhl, Julio Cesar;Carranza, Jaime Moreno, Omar Triana, Edmundo Carlos Grisard. --En: Infection genetics and evolution. -- No.;67 (2002); p. 1-7. -- PONENCIA(S) EN CONGRESO: Caracterizacionantigenicade cepas trypanosoma rangeli;aisladas en ciclos de transmision domestica y silvestre enareasendemicasde Colombia / Carlos Alberto Aya,;Andrea Arevalo, Daniel Urrea, Jorge Garcia, Derly Yara, LeyderE. Lozano,Julio C. Carranza, Gustavo A. -- En:;ARTICULO(S) EN REVISTA: Amplification of a specific repetitiveDNA sequence for trypanosoma rangeli;identification and its potential application in epidemiologicalinvestigations / Nancy Vargas, Ricardo P.;Souto, Julio Cesar Carranza, Gustavo Adolfo Vallejo, Bianca Zingales. -- En: Experimental parasitology. -- No.;96 (2000); p. 147-159. -- Chagas disease and human migration /Felipe Guhl, Carlos Jaramillo, Gustavo Adolfo;Vallejo, Felipe Cardenas, A. Arroyo, Arthur Aufderheide. -'- Vol.95, no. 4(jul.-ago. 2000); p. 553-555. --;Differentiation and genetic analysis of rhodnius prolixusandrhodnius colombiensis by rDNA and RAPD;amplification / Carlos Jaramillo, Maria Fernanda Montaña,LydaRaquel Castro, Gustavo Adolfo Vallejo, Felipe;de la Universidad del Tolima / Julio Cesar Carranza M., LeyderElena Lozano, Gustavo Adolfo Vallejo. -- En:;Sistemas de Informacion Geografica, Sensores Remotos y GeneticaPoblacional de Vectores y Parasitos Aplicados;al Control de la Enfermedad de Chagas / Curso Taller Internacional Sistemas de Informacion Geografica,;Sensores Remotos y Genetica Poblacional de Vectores y ParasitosAplicadosal Control de la Enfermedad de;Chagas (2002 dic. 2-6 : Bogotá) ; Editores Felipe Guhl, CarlosJaramillo.'-- Bogotá : Universidad de Los;Andes, c2002. -- 224 p. : il., mapas, tablas ; 28 cm. -- ISBN9583437021.;Congreso Nacional de Ciencias Biologicas (37 : 2002 oct. 1-4 :San Juan dePasto). -- San Juan de Pasto :;Universidad de Nariño, 2002. -- 28 cm. -- MEMORIA(S): Laboratorio de investigaciones en parasitologia tropica

Phenotype and Reactivity of Lymphocytes Expanded from Benign Prostate Hyperplasic Tissues and Prostate Cancer

Benign prostate hyperplasia (BPH) is a frequent condition in aging men, which affects life quality, causing principally lower urinary tract symptoms. Epidemiologic studies suggest that BPH may raise the risk of developing prostate cancer (PCa), most likely promoting a chronic inflammatory environment. Studies aiming at elucidating the link and risk factors that connect BPH and PCa are urgently needed to develop prevention strategies. The BPH microenvironment, similar to the PCa one, increases immune infiltration of the prostate, but, in contrast to PCa, immunosuppression may not be established yet. In this study, we found that prostate-infiltrating lymphocytes (PILs) expanded from hyperplastic prostate tissue recognized tumor-associated antigens (TAA) and autologous tissue, regardless of the presence of tumor cells. PILs expanded from BPH samples of patients with PCa, however, seem to respond more strongly to autologous tissue. Phenotypic characterization of the infiltrating PILs revealed a trend towards better expanding CD4+ T cells in infiltrates derived from PCa, but no significant differences were found. These findings suggest that T cell tolerance is compromised in BPH-affected prostates, likely due to qualitative or quantitative alterations of the antigenic landscape. Our data support the hypothesis that BPH increases the risk of PCa and may pave the way for new personalized preventive vaccine strategies for these patients

Quantitative and qualitative impairments in dendritic cell subsets of patients with ovarian or prostate cancer

Background Dendritic cells (DCs) are the most efficient antigen-presenting cells, hence initiating a potent and cancer-specific immune response. This ability (mainly using monocyte-derived DCs) has been exploited in vaccination strategies for decades with limited clinical efficacy. Another alternative would be the use of conventional DCs (cDCs) of which at least three subsets circulate in human blood: cDC1s (CD141bright), cDC2s (CD1c+) and plasmacytoid DCs. Despite their paucity, technical advances may allow for their selection and clinical use. However, many assumptions concerning the DC subset biology depend on observations from mouse models, hindering their translational potential. In this study, we characterise human DCs in patients with ovarian cancer (OvC) or prostate cancer (PrC). Patients and methods Whole blood samples from patients with OvC or PrC and healthy donors (HDs) were evaluated by flow cytometry for the phenotypic and functional characterisation of DC subsets. Results In both patient groups, the frequency of total CD141+ DCs was lower than that in HDs, but the cDC1 subset was only reduced in patients with OvC. CD141+ DCs showed a reduced response to the TLR3 agonist poly (I:C) in both groups of patients. An inverse correlation between the frequency of cDC1s and CA125, the OvC tumour burden marker, was observed. Consistently, high expression of CLEC9A in OvC tissue (The Cancer Genome Atlas data set) indicated a better overall survival. Conclusions cDC1s are reduced in patients with OvC, and CD141+ DCs are quantitatively and qualitatively impaired in patients with OvC or PrC. CD141+ DC activation may predict functional impairment. The loss of cDC1s may be a bad prognostic factor for patients with OvC