Tertiary lymphoid structure and neutrophil–lymphocyte ratio coordinately predict outcome of pembrolizumab

Kazumasa Komura, Satoshi Tokushige, Mitsuaki Ishida, Kensuke Hirosuna, Shogo Yamazaki, Kazuki Nishimura, Masahiko Ajiro, Takaya Ohno, Keita Nakamori, Shoko Kinoshita, Takuya Tsujino, Ryoichi Maenosono, Yuki Yoshikawa, Tomoaki Takai, Takeshi Tsutsumi, Kohei Taniguchi, Tomohito Tanaka, Kiyoshi Takahara, Teruo Inamoto, Yoshinobu HiroseFumihito Ono, Yuichi Shiraishi, Akihide Yoshimi, Haruhito Azuma

研究成果: ジャーナルへの寄稿学術論文査読

10 被引用数 (Scopus)

抄録

Emerging evidence suggests that the presence of tertiary lymphoid structures (TLS) and neutrophil–lymphocyte ratio (NLR) in peripheral blood is associated with the treatment response to checkpoint inhibitors (CPIs), whereas there is limited knowledge regarding whether these factors reciprocally impact the treatment outcomes of CPIs in metastatic urothelial carcinoma (mUC). Herein, we investigated treatment outcomes of platinum-refractory mUC patients (50 cases with whole-exome and transcriptome sequencing) treated with pembrolizumab. The pathological review identified 24% of cases of TLS in the specimens. There was no significant difference in the NLR between the TLS− and TLS+ groups (p = 0.153). In the lower NLR group, both overall survival and progression-free survival were significantly longer in patients with TLS than in those without TLS, whereas the favorable outcomes associated with TLS were not observed in patients in the higher NLR group. We explored transcriptomic differences in UC with TLS. The TLS was comparably observed between luminal (20%) and basal (25%) tumor subtypes (p = 0.736). Exploring putative immune-checkpoint genes revealed that ICOSLG (B7-H2) was significantly increased in tumors with lower NLR. KRT expression levels exhibited higher basal cell markers (KRT5 and KRT17) in the higher NLR group and lower differentiated cell markers (KRT8 and KRT18) in patients with TLS. In conclusion, the improved outcomes of pembrolizumab treatment in mUC are restricted to patients with lower NLR. Our findings begin to elucidate a distinct molecular pattern for the presence of TLS according to the NLR in peripheral blood.

本文言語英語
ページ(範囲)4622-4631
ページ数10
ジャーナルCancer science
114
12
DOI
出版ステータス出版済み - 12-2023
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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