PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8(+) T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients.
PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8(+) T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients.
复制标题
DOI：
10.1016/j.ccell.2018.10.007
复制
发表时间：
2018-11-12
期刊：
影响因子：
50.3
通讯作者：
Oft M
中科院分区：
文献类型：
--
作者：
Naing A;Infante JR;Papadopoulos KP;Chan IH;Shen C;Ratti NP;Rojo B;Autio KA;Wong DJ;Patel MR;Ott PA;Falchook GS;Pant S;Hung A;Pekarek KL;Wu V;Adamow M;McCauley S;Mumm JB;Wong P;Van Vlasselaer P;Leveque J;Tannir NM;Oft M
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.
登录
查看更多内容
影响因子：
82.9
作者：
Gros A;Parkhurst MR;Tran E;Pasetto A;Robbins PF;Ilyas S;Prickett TD;Gartner JJ;Crystal JS;Roberts IM;Trebska-McGowan K;Wunderlich JR;Yang JC;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
影响因子：
20.3
作者：
Fujii, S;Shimizu, K;Lotze, MT
通讯作者：
Lotze, MT
影响因子：
15.9
作者：
Cohen, Cyrille J.;Gartner, Jared J.;Robbins, Paul F.
通讯作者：
Robbins, Paul F.
影响因子：
32.4
作者：
Koppelman, B;Neefjes, JJ;Malefyt, RD
通讯作者：
Malefyt, RD