A Potential Mechanism of Anticancer Immune Response Coincident With Immune-related Adverse Events in Patients With Renal Cell Carcinoma

被引：8

作者：

Kato, Taigo ^{[1
,2
]}

Tomiyama, Eisuke ^{[1
]}

Koh, Yoko ^{[1
]}

Matsushita, Makoto ^{[1
]}

Hayashi, Yujiro ^{[1
]}

Nakano, Kosuke ^{[1
]}

Ishizuya, Yu ^{[1
]}

Wang, Cong ^{[1
]}

Hatano, Koji ^{[1
]}

Kawashima, Atsunari ^{[1
]}

Ujike, Takeshi ^{[1
]}

Kawasaki, Keisuke ^{[3
]}

Morii, Eiichi ^{[3
]}

Gotoh, Kunihito ^{[4
]}

Eguchi, Hidetoshi ^{[4
]}

Kiyotani, Kazuma ^{[5
]}

Fujita, Kazutoshi ^{[1
]}

Nonomura, Norio ^{[1
]}

Uemura, Motohide ^{[1
,2
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Urol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Med, Dept Urol Immunooncol, Suita, Osaka, Japan

[3] Osaka Univ, Grad Sch Med, Dept Pathol, Suita, Osaka, Japan

[4] Osaka Univ, Grad Sch Med, Dept Surg Gastroenterol, Suita, Osaka, Japan

[5] Japanese Fdn Canc Res, Canc Precis Med Ctr, Tokyo, Japan

来源：

ANTICANCER RESEARCH | 2020年 / 40卷 / 09期

关键词：

Immune checkpoint inhibitors; immune-related adverse events (irAEs); T-cell receptor; renal cell carcinoma; next-generation sequencing; immune response;

D O I：

10.21873/anticanres.14490

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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, perform 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.

引用

页码：4875 / 4883

页数：9

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