PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8+ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients

被引：209

作者：

Naing, Aung ^{[1
]}

Infante, Jeffrey R. ^{[2
]}

Papadopoulos, Kyriakos P. ^{[3
]}

Chan, Ivan H. ^{[4
]}

Shen, Cong ^{[5
]}

Ratti, Navneet P. ^{[4
]}

Rojo, Bianca ^{[4
]}

Autio, Karen A. ^{[5
]}

Wong, Deborah J. ^{[6
]}

Patel, Manish R. ^{[7
]}

Ott, Patrick A. ^{[8
]}

Falchook, Gerald S. ^{[9
]}

Pant, Shubham ^{[10
]}

Hung, Annie ^{[4
]}

Pekarek, Kara L. ^{[4
]}

Wu, Victoria ^{[4
]}

Adamow, Matthew ^{[5
]}

McCauley, Scott ^{[4
]}

Mumm, John B. ^{[4
]}

Wong, Phillip ^{[5
]}

Van Vlasselaer, Peter ^{[4
]}

Leveque, Joseph ^{[4
]}

Tannir, Nizar M. ^{[1
]}

Oft, Martin ^{[4
]}

机构：

[1] MD Anderson Canc Ctr, Houston, TX USA

[2] PLLC, Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA

[3] START Ctr Canc Care, San Antonio, TX USA

[4] Eli Lilly & Co, ARMO BioSci, Redwood City, CA 94063 USA

[5] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[6] Univ Calif Los Angeles, Los Angeles, CA USA

[7] Sarah Cannon Res Inst Florida Canc Specialists, Sarasota, FL USA

[8] Dana Farber Canc Inst, Boston, MA 02115 USA

[9] Sarah Cannon Res Inst HealthONE, Denver, CO USA

[10] Univ Oklahoma, Oklahoma City, OK USA

来源：

CANCER CELL | 2018年 / 34卷 / 05期

关键词：

EFFECTOR FUNCTION; PD-1; BLOCKADE; TUMOR; INTERLEUKIN-10; SPECIFICITY; RECEPTORS; TOLERANCE; RESPONSES; MELANOMA; DEATH;

D O I：

10.1016/j.ccell.2018.10.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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-y 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.

引用

页码：775 / +

页数：20

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