PEGylated IL-10 (pegilodecakin) induces systemic immune activation, CD8+ T cell invigoration and polyclonal T cell expansion in cancer patients Journal Article


Authors: Naing, A.; Infante, J. R.; Papadopoulos, K. P.; Chan, I. H.; Shen, C.; Ratti, N. P.; Rojo, B.; Autio, K. A.; Wong, D. J.; Patel, M. R.; Ott, P. A.; Falchook, G. S.; Pant, S.; Hung, A.; Pekarek, K. L.; Wu, V.; Adamow, M.; McCauley, S.; Mumm, J. B.; Wong, P.; Van Vlasselaer, P.; Leveque, J.; Tannir, N. M.; Oft, M.
Article Title: PEGylated IL-10 (pegilodecakin) induces systemic immune activation, CD8+ T cell invigoration and polyclonal T cell expansion in cancer patients
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. Naing et al. report that pegilodecakin, PEGylated IL-10, which achieves objective tumor responses in patients, induces hallmarks of CD8+ T cell immunity in cancer patients. Pegilodecakin promotes expansion of underrepresented T cell clones as well as LAG-3+ PD-1+ CD8+ T cells, which are further induced by anti-PD-1. © 2018 Elsevier Inc.
Keywords: clinical article; controlled study; protein phosphorylation; human cell; clinical trial; cancer combination chemotherapy; monotherapy; cancer patient; cd8+ t lymphocyte; lymphocyte proliferation; stat3 protein; cancer immunotherapy; melanoma; multiple cycle treatment; tumor volume; transforming growth factor beta; interleukin 10; interleukin 4; cohort analysis; renal cell carcinoma; granzyme b; th2 cell; cellular immunity; gamma interferon; cd4+ t lymphocyte; single drug dose; upregulation; interleukin 17; th1 cell; cytotoxic t lymphocyte antigen 4; tumor rejection; cell expansion; t lymphocyte activation; tumor necrosis factor; interleukin 12p40; interleukin 18; non small cell lung cancer; clone; clonality; interleukin 23; il-10; clonal expansion; cd8+ t cell; bacterium lipopolysaccharide; drug self administration; polyclonal activation; human; priority journal; article; pembrolizumab; th1; hepatitis a virus cellular receptor 2; am0010; pegilodecakin; pegylated interleukin 10; t cell invigoration; subcutaneous immunotherapy
Journal Title: Cancer Cell
Volume: 34
Issue: 5
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2018-11-12
Start Page: 775
End Page: 791.e3
Language: English
DOI: 10.1016/j.ccell.2018.10.007
PUBMED: 30423297
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Karen Anne Autio
    50 Autio
  2. Phillip Wong
    38 Wong
  3. Matthew J Adamow
    10 Adamow
  4. Cong Shen
    3 Shen