@article{oai:soar-ir.repo.nii.ac.jp:00020225,
 author = {Inoue, Hiroyuki and Park, Jae-Hyun and Kiyotani, Kazuma and Zewde, Makda and Miyashita, Azusa and Jinnin, Masatoshi and Kiniwa, Yukiko and Okuyama, Ryuhei and Tanaka, Ryota and Fujisawa, Yasuhiro and Kato, Hiroshi and Morita, Akimichi and Asai, Jun and Katoh, Norito and Yokota, Kenji and Akiyama, Masashi and Ihn, Hironobu and Fukushima, Satoshi and Nakamura, Yusuke},
 issue = {9},
 journal = {ONCOIMMUNOLOGY},
 month = {Aug},
 note = {Immune checkpoint inhibitors blocking the interaction between programmed death-1 (PD-1) and PD-1 ligand-1 (PD-L1) are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immune-related genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment. We found that, in addition to the PD-L1 (p = 0.03), expression levels of PD-1 ligand-2 (PD-L2), granzyme A (GZMA) and human leukocyte antigen-A (HLA-A) in the pre-treatment tumors were significantly higher (p = 0.04, p = 0.01 and p = 0.006, respectively) in responders (n = 5) than in non-responders (n = 8). With nivolumab treatment, tumors in responders exhibited a substantial increase of CD8, GZMA and perforin 1 (PRF1) expression levels as well as increased ratio of TBX21/GATA3, suggesting dominancy of helper T cell type 1 (Th1) response to type 2 (Th2) response. T cell receptor β (TCR-β) repertoire analysis revealed oligoclonal expansion of tumor-infiltrating T lymphocytes (TILs) in the tumor tissues of the responders. Our findings suggest that melanoma harboring high PD-1 ligands (PD-L1 and PD-L2), GZMA and HLA-A expression may respond preferentially to nivolumab treatment, which can enhance Th1-skewed cellular immunity with oligoclonal expansion of TILs., Article, ONCOIMMUNOLOGY.5(9):e1204507(2016)},
 title = {Intratumoral expression levels of PD-L1, GZMA, and HLA-A along with oligoclonal T cell expansion associate with response to nivolumab in metastatic melanoma},
 volume = {5},
 year = {2016}
}