TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer

被引：316

作者：

Pulido, Alvaro de Mingo ^{[1
]}

Gardner, Alycia ^{[1
,2
]}

Hiebler, Shandi ^{[1
]}

Soliman, Hatem ^{[1
,3
]}

Rugo, Hope S. ^{[4
,5
]}

Krummel, Matthew F. ^{[6
]}

Coussens, Lisa M. ^{[7
,8
]}

Ruffell, Brian ^{[1
,3
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, 12902 Magnolia Dr SRB 2, Tampa, FL 33612 USA

[2] Univ S Florida, Canc Biol PhD Program, Tampa, FL 33620 USA

[3] H Lee Moffitt Canc Ctr & Res Inst, Dept Breast Oncol, Tampa, FL 33612 USA

[4] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA

[7] Oregon Hlth & Sci Univ, Dep Cell Dev & Canc Biol, Portland, OR 97239 USA

[8] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA

来源：

CANCER CELL | 2018年 / 33卷 / 01期

关键词：

CD8(+) T-CELLS; PD-1; BLOCKADE; IMMUNE-RESPONSES; RECEPTOR TIM-3; MURINE MODEL; EXPRESSION; CD8-ALPHA(+); GALECTIN-9; ACTIVATION; EXHAUSTION;

D O I：

10.1016/j.ccell.2017.11.019

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Intratumoral CD103(+) dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103(+) DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8(+) T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors. Gene expression analysis identified upregulation of Cxcl9 within intratumoral DCs during combination therapy, and therapeutic efficacy was ablated by CXCR3 blockade, Batf3 deficiency, or Irf8 deficiency.

引用

页码：60 / +

页数：21

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