KIR Genes and their Ligands Predict the Response to Anti-2 EGFR Monoclonal Antibodies in Solid Tumors

Killer-cell immunoglobulin-like receptors (KIRs) regulate the killing function of NK cells, which play an important role in the antibody-dependent cell-mediated cytotoxicity (ADCC) response exerted by therapeutic monoclonal antibodies (mAbs). However, it is unknown whether the extensive genetic variability of KIR genes and/or their HLA ligands might influence the response to these treatments. This study aimed to explore whether the variability in KIR/HLA genes may be associated to the variable response observed to mAbs-based anti-EGFR therapies. Thirty-nine patients treated with anti-EGFR mAbs (trastuzumab for advanced breast cancer, or cetuximab for advanced colorectal or advanced head and neck cancer), were included in the study. All the patients had progressed to mAbs therapy and were grouped into two categories taking into account time to treatment failure (TTF ≤6 months and TTF ≥10 months). KIR genotyping (16 genetic variability) was performed in genomic DNA from peripheral blood by PCR sequence-specific primer technique and HLA ligand typing was performed for HLA-B & -C loci by reverse PCR-SSO methodology. Subjects carrying the KIR/HLA ligand combinations KIR2DS1/HLAC2C2-C1C2 and KIR3DS1/HLABw4w4-w4w6 showed longer TTF than non-carriers counterparts (14,76 m vs 3,73 m, p<0.001, and 14,93 m vs 4,6 m, p=0.005 respectively). No other significant differences were observed. Two activating KIR/HLA ligand combinations predict better response of patients to anti-EGFR therapy. These findings increase the overall knowledge on the role of specific gene variants related with responsivenessto anti-EGFR treatment in solid tumours and highlight the importance of assessing gene polymorphisms related with cancer medications

The global challenges of the long COVID-19 in adults and children

Institución Universitaria Visión de las Américas. Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Risaralda, Colombia / Universidad Científica del Sur. Faculty of Health Sciences. Lima, Peru / Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Universidad Científica del Sur. Faculty of Health Sciences. Lima, Peru.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Municipal Autonomous Government of Cochabamba. Municipal Secretary of Health. Direction of First Level. Cochabamba, Bolivia.Franz Tamayo University. National Research Coordination. La Paz, Bolivia.Universidad Continental. Research Unit. Huancayo, Peru.Universidad Nacional de Colombia. Department of Pediatrics. Bogotá, DC, Colombia / Fundación HOMI. Hospital Pediátrico La Misericordia. Division of Infectious Diseases. Bogotá, DC, Colombia / Fundación Hospital Infantil Universitario de San José. Bogotá, DC, Colombia.Hemera Unidad de Infectología IPS SAS. Bogota, Colombia.Hospital San Vicente Fundación. Rionegro, Antioquia, Colombia.Clinica Imbanaco Grupo Quironsalud. Cali, Colombia / Universidad Santiago de Cali. Cali, Colombia / Clinica de Occidente. Cali, Colombia / Clinica Sebastián de Belalcazar. Valle del Cauca, Colombia.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina.Universidade Estadual Paulista Júlio de Mesquita Filho. Botucatu Medical School. Infectious Diseases Department. São Paulo, SP, Brazil / Brazilian Society for Infectious Diseases. São Paulo, SP, Brazil.Institute of Infectious Diseases Emilio Ribas. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Pará. Faculdade de Medicina. Belém, PA, Brazil.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina / Hospital de Enfermedades Infecciosas F. J. Muñiz. Buenos Aires, Argentina.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina / Hospital de Enfermedades Infecciosas F. J. Muñiz. Buenos Aires, Argentina.Centro de Referencia de Salud Dr. Salvador Allende Gossens. Policlínico Neurología. Unidad Procedimientos. Santiago de Chile, Chile.Hospital Salvador Bienvenido Gautier. Santo Domingo, Dominican Republic.Universidad Central del Ecuador. Jefatura de Cátedra de Enfermedades Infecciosas. Quito, Ecuador.Universidad Autónoma de Santo Domingo. Santo Domingo, Dominican Republic.Hospital Roosevelt. Guatemala City, GuatemalaNational Autonomous University of Honduras. Institute for Research in Medical Sciences and Right to Health. Tegucigalpa, Honduras.National Clinical Coordinator COVID-19-WHO Studies. Colombia / Universidad Nacional de Colombia. Facultad de Medicina. Clinica Colsanitas. Clinica Universitaria Colombia. Colombia.Think Vaccines LLC. Houston, Texas, USA.Universidad Simón Bolívar. Centro de Investigación en Ciencias de la Vida. Barranquilla, Colombia / Grupo de Expertos Clínicos Secretaria de Salud de Barranquilla. Barranquilla, Colombia.Universidad San Ignacio de Loyola. Vicerrectorado de Investigación. Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud. Lima, Peru.Hospital Evangélico de Montevideo. Montevideo, Uruguay.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia / University of California. School of Public Health. Division of Infectious Diseases and Vaccinology. Berkeley, CA, USA.Universidad Central de Venezuela. Faculty of Medicine. Caracas, Venezuela.Universidad Central de Venezuela. Faculty of Medicine. Caracas, Venezuela / Biomedical Research and Therapeutic Vaccines Institute. Ciudad Bolivar, Venezuela.University of Colorado Anschutz Medical Campus. School of Medicine. Division of Infectious Diseases. Aurora, CO, USA.Tribhuvan University Teaching Hospital. Institute of Medicine. Kathmandu, Nepal / Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth. Dr. D. Y. Patil Medical College. Department of Microbiology. Pune, Maharashtra, India / Dr. D.Y. Patil Dental College and Hospital. Department of Public Health Dentistry. Dr. D.Y. Patil Vidyapeeth, Maharashtra, India.Universidad Cesar Vallejo. Escuela de Medicina. Trujillo, Peru.Universidad de San Martín de Porres. Facultad de Medicina Humana. Chiclayo, Peru.Friedrich Schiller University Jena. Institute of Microbiology. Beutenbergstraße, Jena, Germany / Pontificia Universidad Católica del Ecuador. School of Medicine. Postgraduate Program in Infectious Diseases. Quito, Ecuador.Universidad Simón Bolivar. Faculty of Health Sciences. Barranquilla, Colombia.Johns Hopkins Aramco Healthcare. Specialty Internal Medicine and Quality Department. Dhahran, Saudi Arabia / Indiana University School of Medicine. Department of Medicine. Infectious Disease Division. Indianapolis, IN, USA / Johns Hopkins University School of Medicine. Department of Medicine. Infectious Disease Division. Baltimore, MD, USA.Johns Hopkins Aramco Healthcare. Molecular Diagnostic Laboratory. Dhahran, Saudi Arabia / Alfaisal University. College of Medicine. Riyadh, Saudi Arabia / The University of Haripur. Department of Public Health and Nutrition. Haripur, Pakistan.VM Medicalpark Samsun Hospital. Department of Infectious Diseases. Samsun, Turkey.University of Miami. Miller School of Medicine. Department of Medicine. Division of Infectious Diseases. Miami, FL, USA.Caja Costarricense de Seguro Social. Centro de Ciencias Médicas. Hospital Nacional de Niños Dr. Carlos Sáenz Herrera. Servicio de Infectología Pediátrica. San José, Costa Rica / Instituto de Investigación en Ciencias Médicas. San José, Costa Rica / Universidad de Ciencias Médicas. Facultad de Medicina. Cátedra de Pediatría. San José, Costa Rica