Immunoproteasome expression is associated with better prognosis and response to checkpoint therapies in melanoma

被引：121

作者：

Kalaora, Shelly ^{[1
]}

Lee, Joo Sang ^{[2
,3
]}

Barnea, Eilon ^{[4
]}

Levy, Ronen ^{[1
]}

Greenberg, Polina ^{[1
]}

Alon, Michal ^{[1
]}

Yagel, Gal ^{[1
]}

Bar Eli, Gitit ^{[1
]}

Oren, Roni ^{[5
]}

Peri, Aviyah ^{[1
]}

Patkar, Sushant ^{[2
]}

Bitton, Lital ^{[1
]}

Rosenberg, Steven A. ^{[6
]}

Lotem, Michal ^{[7
]}

Levin, Yishai ^{[8
]}

Admon, Arie ^{[4
]}

Ruppin, Eytan ^{[2
]}

Samuels, Yardena ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Mol Cell Biol, Rehovot, Israel

[2] NCI, Canc Data Sci Lab, Bethesda, MD 20892 USA

[3] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Suwon, South Korea

[4] Technion, Dept Biol, Haifa, Israel

[5] Weizmann Inst Sci, Dept Vet Resources, Rehovot, Israel

[6] NCI, Surg Branch, Bldg 10, Bethesda, MD 20892 USA

[7] Hadassah Med Sch, Sharett Inst Oncol, Jerusalem, Israel

[8] Weizmann Inst Sci, Nancy & Stephen Grand Israel Natl Ctr Personalize, Rehovot, Israel

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

欧洲研究理事会; 欧盟地平线“2020”; 以色列科学基金会;

关键词：

CTLA-4; BLOCKADE; ANTIGEN; CANCER; PROTEASOME; IDENTIFICATION; BINDING; PEPTIDES; TISSUE;

D O I：

10.1038/s41467-020-14639-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Predicting the outcome of immunotherapy treatment in melanoma patients is challenging. Alterations in genes involved in antigen presentation and the interferon gamma (IFN gamma) pathway play an important role in the immune response to tumors. We describe here that the overexpression of PSMB8 and PSMB9, two major components of the immunoproteasome, is predictive of better survival and improved response to immune-checkpoint inhibitors of melanoma patients. We study the mechanism underlying this connection by analyzing the antigenic peptide repertoire of cells that overexpress these subunits using HLA peptidomics. We find a higher response of patient-matched tumor infiltrating lymphocytes against antigens diferentially presented after immunoproteasome overexpression. Importantly, we find that PSMB8 and PSMB9 expression levels are much stronger predictors of melanoma patients' immune response to checkpoint inhibitors than the tumors' mutational burden. These results suggest that PSMB8 and PSMB9 expression levels can serve as important biomarkers for stratifying melanoma patients for immune-checkpoint treatment.

引用

页数：12

共 48 条

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