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 |
| PMCID: | PMC8098754 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 December 2018 -- Source: Scopus |
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