Immune-related adverse events are clustered into distinct subtypes by T-cell profiling before and early after anti-PD-1 treatmentopen access
- Authors
- Kim, Kyung Hwan; Hur, Joon Young; Cho, Jinhyun; Ku, Bo Mi; Koh, Jiae; Koh, June Young; Sun, Jong-Mu; Lee, Se-Noon; Ahn, Jin Seok; Park, Keunchil; Ahn, Myung-Ju; Shin, Eui-Cheol
- Issue Date
- Feb-2020
- Publisher
- TAYLOR & FRANCIS INC
- Keywords
- Immune-related adverse eventanti-PD-1peripheral bloodT cellimmune profilingcancer
- Citation
- ONCOIMMUNOLOGY, v.9, no.1, pp.1 - 12
- Indexed
- SCIE
SCOPUS
- Journal Title
- ONCOIMMUNOLOGY
- Volume
- 9
- Number
- 1
- Start Page
- 1
- End Page
- 12
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/190698
- DOI
- 10.1080/2162402X.2020.1722023
- ISSN
- 2162-402X
- Abstract
- Although anti-programmed death-1 (PD-1) treatment has shown remarkable anti-tumor efficacy, immune-related adverse events (irAEs) develop with heterogeneous clinical manifestations. However, the immunological understanding of irAEs is currently limited. In the present study, we analyzed peripheral blood T cells obtained from cancer patients who received anti-PD-1 treatment to determine the immunological characteristics of irAEs. This study included 31 patients with refractory thymic epithelial tumor (TET) who were enrolled in a phase II trial of pembrolizumab (NCT02607631) and 60 patients with metastatic non-small cell lung cancer (NSCLC) who received pembrolizumab or nivolumab. T-cell profiling was performed by multicolor flow cytometry using peripheral blood obtained before treatment and 7 days after the first dose of anti-PD-1 antibodies. irAEs developed in 21 TET patients and 24 NSCLC patients. Severe (>= grade 3) irAEs occurred in 7 TET patients (22.6%) and 6 NSCLC patients (10.0%). Patients with severe irAEs exhibited a significantly lower fold increase in the frequency of effector regulatory T (eTreg) cells after anti-PD-1 treatment, a higher ratio of T helper-17 (Th17) and T helper-1 cells at baseline, and a higher percentage of Ki-67(+) cells among PD-1(+)CD8(+) T cells posttreatment. In clustering analysis using the T-cell parameters, patients with irAEs were grouped into four distinct subtypes: Th17-related, TNF-related, CD8-related Treg-compensated, and CD8-related Treg-uncompensated. The T-cell parameters showed a predictive value for the development of each subtype of severe irAEs. In conclusion, severe irAEs after anti-PD-1 treatment were clustered into four immunological subtypes, and potential biomarkers for early prediction of severe irAEs were proposed.
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