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J Exp Med ; 217(7)2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32369107

RESUMO

Immune and molecular profiling of CD8 T cells of patients receiving DC vaccines expressing three full-length melanoma antigens (MAs) was performed. Antigen expression levels in DCs had no significant impact on T cell or clinical responses. Patients who received checkpoint blockade before DC vaccination had higher baseline MA-specific CD8 T cell responses but no evidence for improved functional responses to the vaccine. Patients who showed the best clinical responses had low PD-1 expression on MA-specific T cells before and after DC vaccination; however, blockade of PD-1 during antigen presentation by DC had minimal functional impact on PD-1high MA-specific T cells. Gene and protein expression analyses in lymphocytes and tumor samples identified critical immunoregulatory pathways, including CTLA-4 and PD-1. High immune checkpoint gene expression networks correlated with inferior clinical outcomes. Soluble serum PD-L2 showed suggestive positive association with improved outcome. These findings show that checkpoint molecular pathways are critical for vaccine outcomes and suggest specific sequencing of vaccine combinations.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Inibidores de Checkpoint Imunológico/farmacologia , Ativação Linfocitária/imunologia , Antígenos de Neoplasias/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Antígeno CTLA-4/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interferon gama/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Antígeno MART-1/metabolismo , Melanoma/sangue , Melanoma/genética , Melanoma/imunologia , Melanoma/patologia , Receptor de Morte Celular Programada 1/metabolismo , Vacinação
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