Proyectos
Neoadjuvant chemotherapy modulates exhaustion of T cells in breast cancer patients
Resumen
Background: In the world, breast cancer is the leading cause of cancer death in women. The incidence increases linearly with age after 45, with the highest rates after 60, suggesting a link between cancer and aging. With aging, the immune system loses its immunosurveillance capacity associated with increased highly differentiated T cells exhibiting senescence or exhaustion characteristics. This work aimed to evaluate the effect of neoadjuvant chemotherapy on the expression of exhaustion and senescence markers in T cells in women with breast cancer. Methods: We took peripheral blood samples from women with breast cancer at the time of diagnosis and after neoadjuvant chemotherapy and healthy women of the same age as controls. T cells were analyzed in ex-vivo and in-vitro assays using multiparametric flow cytometry. Data were analyzed manually and tSNE, FlowSOM, and CITRUS algorithms. The ethics committee from the National University of Colombia Faculty of Medicine approved this research project Results: T cells from women with breast cancer showed functional and phenotypic alteration such as: (i) less capacity to respond to in-vitro stimulation, and (ii) increased senescence and exhaustion-associated markers as TIM-3, LAG3, and CD57. After neoadjuvant chemotherapy, we found changes associated with immunomodulation and recovery capacity to respond to in-vitro stimulation. These results were confirmed by unsupervised analysis (CITRUS). Conclusions: This study showed changes in T cells in breast cancer patients associated with dysfunction and expression of senescence and exhaustion markers. Furthermore, our findings coincide with other studies that indicate that chemotherapy induces the reactivation of immunosurveillance.
Convocatoria
Nombre de la convocatoria:CONVOCATORIA PERMANENTE PARA EDICIÓN DE TEXTOS EN INGLÉS DESTINADOS A PUBLICACIONES CIENTIFICAS SOMETIDAS A REVISTAS INTERNACIONALES DE ALTO IMPACTO, PRESENTADAS POR DOCENTES DE PLANTA, INVESTIGADORES Y ESTUDIANTES DE POSGRADO.
Modalidad:Modalidad única
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