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Abstract Introduction: The progress made in cancer immunotherapy and the clinical response of patients who have undergone this type of therapy have made it the fourth pillar of cancer treatment. Objective: To briefly describe the biological rationale of personalized neoantigen-based cancer immunotherapy, the current perspectives regarding its development, and some of the clinical outcomes achieved with this therapy. Materials and methods: A literature search was performed in PubMed, Scopus and EBSCO using the following search strategy: type of articles: original experimental studies, clinical trials, and narrative and systematic reviews addressing methods to identify mutations found in tumors and cancer immunotherapy strategies based on neoantigen-based vaccines; study population: humans and animal models; publication period: January 1989 - December 2019; language: English and Spanish; search terms: "Immunotherapy", "Neoplasms", "Mutation" and "Cancer Vaccines". Results: The initial search started with 1 344 records. Once duplicates were removed (n=176), 780 studies were excluded after reading their abstract and title. The full text of 338 articles was read to confirm which met the inclusion criteria, finally including 73 studies for full analysis. All articles retrieved were published in English and were mainly conducted in the USA (43.83%) and Germany (23.65%). In the case of original studies (n=43), 20 were performed in humans only, 9 in animals only, 2 in both models, and 12 used in silico methodology. Conclusion: Personalized cancer immunotherapy with tumor neoantigen-based vaccines is strongly emerging as a new alternative to treat cancer. However, to achieve its appropriate implementation, it is necessary to use it in combination with conventional treatments, produce more knowledge that helps clarify cancer immunobiology, and reduce the costs associated with its production.
Resumen Introducción. Los avances que se han hecho en inmunoterapia contra el cáncer y la respuesta clínica de los pacientes que han recibido este tipo de terapia la han convertido en el cuarto pilar para el tratamiento del cáncer. Objetivo. Describir brevemente el fundamento biológico de la inmunoterapia personalizada contra el cáncer basada en neoantígenos, las perspectivas actuales de su desarrollo y algunos resultados clínicos de esta terapia. Materiales y métodos. Se realizó una búsqueda de la literatura en PubMed, Scopus y EBSCO utilizando la siguiente estrategia de búsqueda: tipo de artículos: estudios experimentales originales, ensayos clínicos y revisiones narrativas y sistemáticas sobre métodos de identificación de mutaciones generadas en los tumores y estrategias de inmunoterapia del cáncer con vacunas basadas en neoantígenos; población de estudio: humanos y modelos animales; periodo de publicación: enero de 1989 a julio de 2019; idioma: inglés y español; términos de búsqueda: "Immunotherapy", "Neoplasms", "Mutation" y "Cancer Vaccines". Resultados. La búsqueda inicial arrojó 1 344 registros; luego de remover duplicados (n = 176), 780 fueron excluidos después de leer su resumen y título, y se evaluó el texto completo de 338 para verificar cuáles cumplían con los criterios de inclusión, seleccionándose finalmente 73 estudios para análisis completo. Todos los artículos recuperados se publicaron en inglés, y fueron realizados principalmente en EE. A (43.83%) y Alemania (23.65%). En el caso de los estudios originales (n=43), 20 se realizaron únicamente en humanos, 9 solo en animales, 2 en ambos modelos, y 12 usaron metodología in silico. Conclusión. La inmunoterapia personalizada contra el cáncer con vacunas basadas en neoantígenos tumorales se está convirtiendo de forma contundente en una nueva alternativa para tratar el cáncer. Sin embargo, para lograr su implementación adecuada, es necesario usarla en combinación con tratamientos convencionales, generar más conocimiento que contribuya a aclarar la inmunobiología del cáncer y reducir los costos asociados con su producción.
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Background: Aging is accompanied by alterations in immune response which leads to increased susceptibility to infectious diseases, cancer, autoimmunity, and inflammatory disorders. This decline in immune function is termed as immunosenescence; however, the mechanisms are not fully elucidated. Experimental approaches of adaptive immunity, particularly for T cells, have been the main focus of immunosenescence research. This systematic review evaluates and discusses T cell markers implicated in immunosenescence. Objective: To determine the best flow cytometry markers of circulating T cells associated with immunosenescence. Methods: We systematically queried PubMed, MEDLINE, EBSCO, and BVS databases for original articles focused on two age groups of healthy humans: 18-44 (young adults) and >60 (older adults) years. In accordance with the Cochrane methodology, we synthesized data through qualitative descriptions and quantitative random effects meta-analysis due to extensive heterogeneity. Results: A total of 36 studies conducted in the last 20 years were included for the qualitative analysis and four out of these studies were used to perform the meta-analysis. A significant decrease in naïve T cell subset was observed in older adults compared to young adults. Primary markers used to identify senescent cells were loss of CD28 and increased expression of CD57 and KLRG1 in terminally-differentiated memory T cell subset in older adults. Moreover, we observed an increase in proinflammatory cytokines and decrease in telomere length in old adult T cells. It was not possible to perform quantitative synthesis on cell markers, cytokines, and telomere length because of the significant variations between the groups, which is attributed to differences in protocols and unreported measurements, thus generating a high risk of bias. Conclusions: Heterogeneity among studies in terms of data report, measurement techniques and high risk of bias were major impediments for performing a robust statistical analysis that could aid the identification of eligible flow cytometry markers of immunosenescence phenotype in T cells.
