Understanding adverse events of immunotherapy: A mechanistic perspective

被引：27

作者：

Burke, Kelly P. ^{[1
,2
,3
,4
,5
]}

Grebinoski, Stephanie ^{[7
,8
]}

Sharpe, Arlene H. ^{[3
,4
,5
,6
]}

Vignali, Dario A. A. ^{[7
,9
,10
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Harvard Med Sch, Blavatnik Inst, Dept Immunol, Boston, MA 02115 USA

[4] Harvard Med Sch, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[6] Broad Inst MIT & Harvard Univ, Cambridge, MA 02115 USA

[7] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA 15213 USA

[8] Univ Pittsburgh, Sch Med, Grad Program Microbiol & Immunol, Pittsburgh, PA USA

[9] UPMC Hillman Canc Ctr, Tumor Microenvironm Ctr, Pittsburgh, PA 15232 USA

[10] UPMC Hillman Canc Ctr, Canc Immunol & Immunotherapy Program, Pittsburgh, PA 15232 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2021年 / 218卷 / 01期

基金：

美国国家卫生研究院;

关键词：

CANCER; PATHWAYS;

D O I：

10.1084/jem.20192179

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The treatment of many cancers has been revolutionized by immune checkpoint blockade (ICB) as a standard-of-care therapeutic. Despite many successes, a large proportion of patients treated with ICB agents experience immune-related adverse events (irAEs) in the form of clinical autoimmunity, ranging from mild to life threatening, that can limit cancer treatment. A mechanistic understanding of these irAEs is required to better treat or prevent irAEs and to predict those patients who are susceptible to irAEs. We propose several mechanisms that may contribute to the generation of irAEs: (1) preexisting susceptibility to autoimmunity, (2) aberrant presentation of "self" by the tumor, and (3) loss of tolerance driven by the tumor or tissue microenvironment.

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页数：6

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