PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8+ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients.
Cancer Cell
; 34(5): 775-791.e3, 2018 11 12.
Article
em En
| MEDLINE
| ID: mdl-30423297
ABSTRACT
Tumor-reactive T cell exhaustion prevents the success of immune therapies. Pegilodecakin activates intratumoral CD8+ T cells in mice and induces objective tumor responses in patients. Here we report that pegilodecakin induces hallmarks of CD8+ T cell immunity in cancer patients, including elevation of interferon-γ and GranzymeB, expansion and activation of intratumoral CD8+ T cells, and proliferation and expansion of LAG-3+ PD-1+ CD8+ T cells. On pegilodecakin, newly expanded T cell clones, undetectable at baseline, become 1%-10% of the total T cell repertoire in the blood. Elevation of interleukin-18, expansion of LAG-3+ PD-1+ T cells and novel T cell clones each correlated with objective tumor responses. Combined pegilodecakin with anti-PD-1 increased the expansion of LAG-3+ PD-1+ CD8+ T cells.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
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Ativação Linfocitária
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Linfócitos do Interstício Tumoral
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Interleucina-10
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Linfócitos T CD8-Positivos
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Imunoterapia
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Neoplasias
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article