Multi-omic profiling reveals discrepant immunogenic properties and a unique tumor microenvironment among melanoma brain metastases

被引：11

作者：

In, Gino K. ^{[1
]}

Ribeiro, Jennifer R. ^{[2
]}

Yin, Jun ^{[2
]}

Xiu, Joanne ^{[2
]}

Bustos, Matias A. ^{[3
]}

Ito, Fumito ^{[4
]}

Chow, Frances ^{[5
,6
]}

Zada, Gabriel ^{[6
]}

Hwang, Lindsay ^{[7
,8
]}

Salama, April K. S. ^{[9
]}

Park, Soo J. ^{[10
]}

Moser, Justin C. ^{[11
]}

Darabi, Sourat ^{[12
]}

Domingo-Musibay, Evidio ^{[13
]}

Ascierto, Maria L. ^{[14
]}

Margolin, Kim ^{[15
]}

Lutzky, Jose ^{[16
]}

Gibney, Geoffrey T. ^{[17
]}

Atkins, Michael B. ^{[18
]}

Izar, Benjamin ^{[19
]}

Hoon, Dave S. B. ^{[3
]}

Vanderwalde, Ari M. ^{[20
,21
]}

机构：

[1] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Div Oncol, Los Angeles, CA 90007 USA

[2] Caris Life Sci, Phoenix, AZ USA

[3] St Johns Canc Inst, Providence St Johns Hlth Ctr, Dept Translat Mol Med, Santa Monica, CA USA

[4] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Surg, Los Angeles, CA USA

[5] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Neurol, Los Angeles, CA USA

[6] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Neurol Surg, Los Angeles, CA USA

[7] LAC USC Med Ctr, Los Angeles, CA USA

[8] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Radiat Oncol, Los Angeles, CA USA

[9] Duke Univ, Duke Canc Inst, Div Med Oncol, Durham, NC USA

[10] Univ Calif San Diego, Moores Canc Ctr, Div Hematol Oncol, La Jolla, CA USA

[11] HonorHealth Res & Innovat Inst, Scottsdale, AZ USA

[12] Hoag Hosp, Hoag Family Canc Inst, Newport Beach, CA USA

[13] Univ Minnesota, Med Sch, Masonic Canc Ctr, Dept Med, Minneapolis, MN USA

[14] St Johns Canc Inst, Providence St Johns Hlth Ctr, Dept Translat Immunol, Rosalie & Harold Rae Brown Canc Immunotherapy Res, Santa Monica, CA USA

[15] St Johns Canc Inst, Providence St Johns Hlth Ctr, Dept Med Oncol, Santa Monica, CA USA

[16] Univ Miami Hlth Syst, Sylvester Comprehens Canc Ctr, Miami, FL USA

[17] Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Div Hematol & Oncol, Washington, DC USA

[18] Georgetown Lombardi Comprehens Canc Ctr, Georgetown, WA USA

[19] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA

[20] Caris Life Sci, Irving, TX USA

[21] West Canc Ctr & Res Inst, 514 Chickasawba St, Blytheville, AR 72315 USA

来源：

NPJ PRECISION ONCOLOGY | 2023年 / 7卷 / 01期

关键词：

OXIDATIVE-PHOSPHORYLATION; MITOCHONDRIAL BIOGENESIS; GENETIC ALTERATIONS; COMBINED NIVOLUMAB; B-CELLS; EXPRESSION; RESISTANCE; PTEN; PATHWAY; IMMUNOTHERAPY;

D O I：

10.1038/s41698-023-00471-z

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort. MBM exhibited lower interferon-gamma (IFN gamma) scores and T cell-inflamed scores compared to primary cutaneous melanoma (PCM) or extracranial metastases (ECM), which was independent of tumor mutational burden. Among MBM, there were fewer computationally inferred immune cell infiltrates, which correlated with lower TNF and IL12B mRNA levels. Ingenuity pathway analysis (IPA) revealed suppression of inflammatory responses and dendritic cell maturation pathways. MBM also demonstrated a higher frequency of pathogenic PTEN mutations and angiogenic signaling. Oxidative phosphorylation (OXPHOS) was enriched in MBM and negatively correlated with NK cell and B cell-associated transcriptomic signatures. Modulating metabolic or angiogenic pathways in MBM may improve responses to immunotherapy in this difficult-to-treat patient subset.

引用

页数：10

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