PT  - JOURNAL ARTICLE
AU  - TAIGO KATO
AU  - EISUKE TOMIYAMA
AU  - YOKO KOH
AU  - MAKOTO MATSUSHITA
AU  - YUJIRO HAYASHI
AU  - KOSUKE NAKANO
AU  - YU ISHIZUYA
AU  - CONG WANG
AU  - KOJI HATANO
AU  - ATSUNARI KAWASHIMA
AU  - TAKESHI UJIKE
AU  - KEISUKE KAWASAKI
AU  - EIICHI MORII
AU  - KUNIHITO GOTOH
AU  - HIDETOSHI EGUCHI
AU  - KAZUMA KIYOTANI
AU  - KAZUTOSHI FUJITA
AU  - NORIO NONOMURA
AU  - MOTOHIDE UEMURA
TI  - A Potential Mechanism of Anticancer Immune Response Coincident With Immune-related Adverse Events in Patients With Renal Cell Carcinoma
AID  - 10.21873/anticanres.14490
DP  - 2020 Sep 01
TA  - Anticancer Research
PG  - 4875--4883
VI  - 40
IP  - 9
4099  - http://ar.iiarjournals.org/content/40/9/4875.short
4100  - http://ar.iiarjournals.org/content/40/9/4875.full
SO  - Anticancer Res2020 Sep 01; 40
AB  - Background/Aim: Some reports showed encouraging efficacy of immune checkpoint inhibitors among patients who experienced immune-related adverse events (irAEs). Thus, characterization of T-cell repertoire and immune signatures in peripheral blood mononuclear cells (PBMCs) and tumors before and after immune checkpoint inhibitors treatment should contribute to better understanding of irAE-provoked anticancer immune responses. Materials and Methods: We applied expression analysis of immune-related genes and T-cell receptor sequencing in tumor and PBMCs from five patients with renal cell carcinoma before combined immunotherapy and at the onset of severe irAEs. Results: We found that the cluster of differentiation 8 (CD8)/forkhead box P3(FOXP3), granzyme B(GZMB)/CD3, perforin 1(PRF1)/CD3 and programmed cell death 1(PD1)/CD8 expression ratios were significantly elevated in PBMCs at the onset of irAEs. In addition, we found expansion of certain T-cell clones in metastatic tissue after irAEs, which were already increased in peripheral blood at the onset of irAEs. Conclusion: irAE-provoked T-cells may also circulate and attack distant tumors, leading to durable response in patients with irAEs.