RESUMO
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 (Assuntos
Desoxicitidina
, Gencitabina
, Imunoterapia
, Terapia Neoadjuvante
, Neoplasias da Bexiga Urinária
, Humanos
, Neoplasias da Bexiga Urinária/tratamento farmacológico
, Neoplasias da Bexiga Urinária/imunologia
, Neoplasias da Bexiga Urinária/terapia
, Neoplasias da Bexiga Urinária/patologia
, Terapia Neoadjuvante/métodos
, Desoxicitidina/análogos & derivados
, Desoxicitidina/uso terapêutico
, Desoxicitidina/administração & dosagem
, Imunoterapia/métodos
, Masculino
, Cisplatino/uso terapêutico
, Cisplatino/administração & dosagem
, Feminino
, Anticorpos Monoclonais Humanizados/uso terapêutico
, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
, Inibidores de Checkpoint Imunológico/uso terapêutico
, Idoso
, Pessoa de Meia-Idade
, Invasividade Neoplásica
, Interleucina-9/metabolismo
, Antígeno B7-H1/metabolismo
, Biomarcadores Tumorais/sangue
, Resultado do Tratamento
RESUMO
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.