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

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.

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.

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.

irAE-provoked T-cells may also circulate and attack distant tumors, leading to durable response in patients with irAEs.

Anticancer research. 2020 Sep [Epub]

Taigo Kato, Eisuke Tomiyama, Yoko Koh, Makoto Matsushita, Yujiro Hayashi, Kosuke Nakano, Y U Ishizuya, Cong Wang, Koji Hatano, Atsunari Kawashima, Takeshi Ujike, Keisuke Kawasaki, Eiichi Morii, Kunihito Gotoh, Hidetoshi Eguchi, Kazuma Kiyotani, Kazutoshi Fujita, Norio Nonomura, Motohide Uemura

Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan ., Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan., Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan., Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan., Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.