Multi-omics Profiling of Patients with Melanoma Treated with Nivolumab in Project HOPE.
Project HOPE (High-tech Omics-based Patient Evaluation) has been in progress since 2014 and uses whole-exome sequencing (WES) and gene expression profiling (GEP). Among a total of 1,685 patients with cancer, 13 with melanoma were registered and characterized using multi-omics analyses to investigate specific biomarkers in responders to programmed cell death-1 (PD-1) blockade.



The patients with melanoma comprised of six males and seven females, and their mean age was 68 years. Five patients were treated with nivolumab, and two were responders.



GEP analysis demonstrated that PD-L1 expression was positive in for cases, and melanoma-associated antigens and tumor signaling-associated genes were up-regulated in tumor compared with normal tissues. Additionally, WES analysis indicated more single nucleotide variants (SNVs) per melanoma tumor compared to other tumor types. Remarkably, a case of complete remission after nivolumab therapy showed high expression of PD-L1 protein and the highest number of SNVs.



The novel approach used in Project HOPE might be an efficient tool that facilitates identifying specific biomarkers predictive of good responders to anti-PD-1 therapy.
Division of Dermatology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Shusuke
S
Yoshikawa
Division of Dermatology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Yoshio
Y
Kiyohara
Division of Dermatology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Masaki
M
Otsuka
Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Ryota
R
Kondou
Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Chizu
C
Nonomura
Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Haruo
H
Miyata
Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Akira
A
Iizuka
Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Keiichi
K
Ohshima
Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Kenichi
K
Urakami
SRL Inc., Tokyo, Japan.
Takeshi
T
Nagashima
Regional Resources Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Masatoshi
M
Kusuhara
Division of Pathology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Takashi
T
Sugino
Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Tohru
T
Mochizuki
Office of the President, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Ken
K
Yamaguchi
Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan y.akiyama@scchr.jp.
Yasuto
Y
Akiyama
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D060890:B7-H1 Antigen / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007564:Japan; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D000077594:Nivolumab; D020641:Polymorphism, Single Nucleotide; D012074:Remission Induction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D000077594:Nivolumab
GEP; Japanese melanoma; SNV; WES; gene expression profiling; immune checkpoint antibody; single nucleotide variant; whole-exome sequencing