RESUMEN
Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC). Immune checkpoint inhibition (ICI) alone, and ICI in combination with chemotherapy, have demonstrated promising pathologic response (Asunto(s)
Desoxicitidina
, Gemcitabina
, Inmunoterapia
, Terapia Neoadyuvante
, Neoplasias de la Vejiga Urinaria
, Humanos
, Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
, Neoplasias de la Vejiga Urinaria/inmunología
, Neoplasias de la Vejiga Urinaria/terapia
, Neoplasias de la Vejiga Urinaria/patología
, Terapia Neoadyuvante/métodos
, Desoxicitidina/análogos & derivados
, Desoxicitidina/uso terapéutico
, Desoxicitidina/administración & dosificación
, Inmunoterapia/métodos
, Masculino
, Cisplatino/uso terapéutico
, Cisplatino/administración & dosificación
, Femenino
, Anticuerpos Monoclonales Humanizados/uso terapéutico
, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
, Inhibidores de Puntos de Control Inmunológico/uso terapéutico
, Anciano
, Persona de Mediana Edad
, Invasividad Neoplásica
, Interleucina-9/metabolismo
, Antígeno B7-H1/metabolismo
, Biomarcadores de Tumor/sangre
, Resultado del Tratamiento
RESUMEN
In people with HIV (PWH), the post-antiretroviral therapy (ART) window is critical for immune restoration and HIV reservoir stabilization. We employ deep immune profiling and T cell receptor (TCR) sequencing and examine proliferation to assess how ART impacts T cell homeostasis. In PWH on long-term ART, lymphocyte frequencies and phenotypes are mostly stable. By contrast, broad phenotypic changes in natural killer (NK) cells, γδ T cells, B cells, and CD4+ and CD8+ T cells are observed in the post-ART window. Whereas CD8+ T cells mostly restore, memory CD4+ T subsets and cytolytic NK cells show incomplete restoration 1.4 years post ART. Surprisingly, the hierarchies and frequencies of dominant CD4 TCR clonotypes (0.1%-11% of all CD4+ T cells) remain stable post ART, suggesting that clonal homeostasis can be independent of homeostatic processes regulating CD4+ T cell absolute number, phenotypes, and function. The slow restoration of host immunity post ART also has implications for the design of ART interruption studies.