PURPOSE: To analyze tumor-microenvironment relationships in Hodgkin lymphoma (HL) as potential determinants in the decision-making process related to the alterations in cell cycle and apoptotic pathways of Hodgkin/Reed-Sternberg (H/RS) cells. EXPERIMENTAL DESIGN: Based on a cohort of 257 classic HL patients, we carried out a global descriptive correlational analysis and logistic regression study to identify tumor-infiltrated immune cell rate in HL that could be interconnected with genes involved in the regulation of apoptotic/proliferative pathways in H/RS cells. RESULTS: Our results reveal the existence of a connection between the reactive microenvironment and molecular changes in apoptotic/proliferative pathways in H/RS cells. A lesser incidence of infiltrated cytotoxic cells in the tumor (CD8(+) T lymphocytes, CD57(+) natural killer, and granzyme B(+) cells) was associated with overexpression of antiapoptotic proteins (Bcl-X(L), survivin, caspase-3, and nuclear factor-kappaB) in tumoral cells. Increased incidence of general infiltrated immune cells, such as CD4(+) T lymphocytes, CD57(+) natural killer cells, activated CTL, and dendritic cells, in the microenvironment of the tumor was associated with increased growth fraction of tumoral cells, including G(1)-S checkpoint (cyclin D and cyclin E) and tumor suppressor pathways (p16 and SKP2), and with the presence of EBV (signal transducers and activators of transcription 1 and 3 expression; STAT1/STAT3). CONCLUSIONS: A lower level of cytotoxic cells correlated with an increase of antiapoptotic mechanisms in H/RS cells, whereas the global infiltrated immune population correlated with the growth fraction of the tumor. Our collective data suggest a causal relationship between infiltrated immune response and concurrent changes of the different proliferative checkpoints, tumor suppressor, and apoptotic pathways of H/RS cells in HL.
PURPOSE: To analyze tumor-microenvironment relationships in Hodgkin lymphoma (HL) as potential determinants in the decision-making process related to the alterations in cell cycle and apoptotic pathways of Hodgkin/Reed-Sternberg (H/RS) cells. EXPERIMENTAL DESIGN: Based on a cohort of 257 classic HL patients, we carried out a global descriptive correlational analysis and logistic regression study to identify tumor-infiltrated immune cell rate in HL that could be interconnected with genes involved in the regulation of apoptotic/proliferative pathways in H/RS cells. RESULTS: Our results reveal the existence of a connection between the reactive microenvironment and molecular changes in apoptotic/proliferative pathways in H/RS cells. A lesser incidence of infiltrated cytotoxic cells in the tumor (CD8(+) T lymphocytes, CD57(+) natural killer, and granzyme B(+) cells) was associated with overexpression of antiapoptotic proteins (Bcl-X(L), survivin, caspase-3, and nuclear factor-kappaB) in tumoral cells. Increased incidence of general infiltrated immune cells, such as CD4(+) T lymphocytes, CD57(+) natural killer cells, activated CTL, and dendritic cells, in the microenvironment of the tumor was associated with increased growth fraction of tumoral cells, including G(1)-S checkpoint (cyclin D and cyclin E) and tumor suppressor pathways (p16 and SKP2), and with the presence of EBV (signal transducers and activators of transcription 1 and 3 expression; STAT1/STAT3). CONCLUSIONS: A lower level of cytotoxic cells correlated with an increase of antiapoptotic mechanisms in H/RS cells, whereas the global infiltrated immune population correlated with the growth fraction of the tumor. Our collective data suggest a causal relationship between infiltrated immune response and concurrent changes of the different proliferative checkpoints, tumor suppressor, and apoptotic pathways of H/RS cells in HL.
Authors: Beatriz Sánchez-Espiridión; Ana M Martín-Moreno; Carlos Montalbán; Vianihuini Figueroa; Francisco Vega; Anas Younes; L Jeffrey Medeiros; Francisco J Alvés; Miguel Canales; Mónica Estévez; Javier Menarguez; Pilar Sabín; María C Ruiz-Marcellán; Andrés Lopez; Pedro Sánchez-Godoy; Fernando Burgos; Carlos Santonja; José L López; Miguel A Piris; Juan F Garcia Journal: Br J Haematol Date: 2013-06-01 Impact factor: 6.998
Authors: Luis de la Cruz-Merino; Marylène Lejeune; Esteban Nogales Fernández; Fernando Henao Carrasco; Ana Grueso López; Ana Illescas Vacas; Mariano Provencio Pulla; Cristina Callau; Tomás Álvaro Journal: Clin Dev Immunol Date: 2012-08-15
Authors: Tomás Alvaro; Luis de la Cruz-Merino; Fernando Henao-Carrasco; José Luis Villar Rodríguez; David Vicente Baz; Manuel Codes Manuel de Villena; Mariano Provencio Journal: J Biomed Biotechnol Date: 2010-08-12
Authors: Alessandra Romano; Calogero Vetro; Giovanni Caocci; Marianna Greco; Nunziatina Laura Parrinello; Francesco Di Raimondo; Giorgio La Nasa Journal: Mediterr J Hematol Infect Dis Date: 2014-06-01 Impact factor: 2.576