Integrative Tumor and Immune Cell Multi-omic Analyses Predict Response to Immune Checkpoint Blockade in Melanoma

被引：63

作者：

Anagnostou, Valsamo ^{[1
,2
]}

Bruhm, Daniel C. ^{[1
]}

Niknafs, Noushin ^{[1
]}

White, James R. ^{[1
]}

Shao, Xiaoshan M. ^{[1
]}

Sidhom, John William ^{[1
,2
]}

Stein, Julie ^{[2
,3
]}

Tsai, Hua-Ling ^{[1
]}

Wang, Hao ^{[1
]}

Belcaid, Zineb ^{[1
,2
]}

Murray, Joseph ^{[1
,2
]}

Balan, Archana ^{[1
]}

Ferreira, Leonardo ^{[1
]}

Ross-Macdonald, Petra ^{[4
]}

Wind-Rotolo, Megan ^{[4
]}

Baras, Alexander S. ^{[2
,3
]}

Taube, Janis ^{[2
,3
]}

Karchin, Rachel ^{[1
]}

Scharpf, Robert B. ^{[1
]}

Grasso, Catherine ^{[5
,6
]}

Ribas, Antoni ^{[5
,7
]}

Pardoll, Drew M. ^{[1
,2
]}

Topalian, Suzanne L. ^{[1
,2
,8
]}

Velculescu, Victor E. ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Bloomberg Kimmel Inst Canc Immunotherapy, Sch Med, Baltimore, MD 21287 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA

[4] Bristol Myers Squibb Co, Princeton, NJ 08540 USA

[5] Univ Calif Los Angeles UCLA, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA

[6] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[7] Parker Inst Canc Immunotherapy, San Francisco, CA USA

[8] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21287 USA

来源：

CELL REPORTS MEDICINE | 2020年 / 1卷 / 08期

基金：

美国国家卫生研究院;

关键词：

MHC CLASS-I; B-CELLS; COMBINED NIVOLUMAB; PD-1; BLOCKADE; LUNG-CANCER; IMMUNOTHERAPY; RESISTANCE; SURVIVAL; IPILIMUMAB; EXPRESSION;

D O I：

10.1016/j.xcrm.2020.100139

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

In this study, we incorporate analyses of genome-wide sequence and structural alterations with pre- and ontherapy transcriptomic and T cell repertoire features in immunotherapy-naive melanoma patients treated with immune checkpoint blockade. Although tumor mutation burden is associated with improved treatment response, the mutation frequency in expressed genes is superior in predicting outcome. Increased T cell density in baseline tumors and dynamic changes in regression or expansion of the T cell repertoire during therapy distinguish responders from non-responders. Transcriptome analyses reveal an increased abundance of B cell subsets in tumors from responders and patterns of molecular response related to expressed mutation elimination or retention that reflect clinical outcome. High-dimensional genomic, transcriptomic, and immune repertoire data were integrated into a multi-modal predictor of response. These findings identify genomic and transcriptomic characteristics of tumors and immune cells that predict response to immune checkpoint blockade and highlight the importance of pre-existing T and B cell immunity in therapeutic outcomes.

引用

页数：19

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