Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities

immuneACCESS ◽  
2019 ◽  
Author(s):  
SK Subudhi ◽  
A Aparicio ◽  
J Gao ◽  
AJ Zurita ◽  
JC Araujo ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Clonal Expansion ◽  
Systemic Circulation

scholarly journals Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities

2016 ◽  
Vol 113 (42) ◽  
pp. 11919-11924 ◽  
Author(s):  
Sumit K. Subudhi ◽  
Ana Aparicio ◽  
Jianjun Gao ◽  
Amado J. Zurita ◽  
John C. Araujo ◽  
...  
Keyword(s):  
T Cells ◽  
Early Intervention ◽  
T Cell ◽  
Cd8 T Cells ◽  
Clonal Expansion ◽  
Cd8 T Cell ◽  
Systemic Circulation ◽  
Blood Samples ◽  
Cell Responses ◽  
Cell Clones

Immune checkpoint therapies, such as ipilimumab, induce dramatic antitumor responses in a subset of patients with advanced malignancies, but they may also induce inflammatory responses and toxicities termed immune-related adverse events (irAEs). These irAEs are often low grade and manageable, but severe irAEs may lead to prolonged hospitalizations or fatalities. Early intervention is necessary to minimize morbidities that occur with severe irAEs. However, correlative biomarkers are currently lacking. In a phase II clinical trial that treated 27 patients with metastatic prostate cancer, we aimed to test the safety and efficacy of androgen deprivation therapy plus ipilimumab. In this study, we observed grade 3 toxicities in >40% of treated patients, which led to early closure of the study. Because ipilimumab enhances T-cell responses, we hypothesized that increased clonal T-cell responses in the systemic circulation may contribute to irAEs. Sequencing of the T-cell receptor β-chains in purified T cells revealed clonal expansion of CD8 T cells, which occurred in blood samples collected before the onset of grade 2–3 irAEs. These initial results suggested that expansion of ≥55 CD8 T-cell clones preceded the development of severe irAEs. We further evaluated available blood samples from a second trial and determined that patients who experienced grade 2–3 irAEs also had expansion of ≥55 CD8 T-cell clones in blood samples collected before the onset of irAEs. We propose that CD8 T-cell clonal expansion may be a correlative biomarker to enable close monitoring and early intervention for patients receiving ipilimumab.

scholarly journals The Roles of IL-12 in Providing a Third Signal for Clonal Expansion of Naive CD8 T Cells

2002 ◽  
Vol 169 (12) ◽  
pp. 6842-6849 ◽  
Author(s):  
Javier Valenzuela ◽  
Clint Schmidt ◽  
Matthew Mescher
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Clonal Expansion

scholarly journals Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI

2021 ◽  
Author(s):  
Christian R Schultze-Florey ◽  
Leonie Kuhlmann ◽  
Solaiman Raha ◽  
Joana Barros-Martins ◽  
Ivan Odak ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
Prospective Clinical Study ◽  
Hematopoietic Stem ◽  
Graft Versus Leukemia ◽  
Αβ T Cells ◽  
Durable Remission

Donor lymphocyte infusion (DLI) is a standard of care for relapse of AML after allogeneic hematopoietic stem cell transplantation (aHSCT). Currently it is poorly understood how and when CD8+ αβ T cells exert graft-versus-leukemia (GvL) activity after DLI. Also, there is no reliable biomarker to monitor GvL activity of the infused CD8+ T cells. Therefore, we analyzed the dynamics of CD8+ αβ T cell clones in DLI-patients. In this prospective clinical study of 29 patients, we performed deep T cell receptor β (TRB) sequencing of sorted CD8+ αβ T cells to track patients' repertoire changes in response to DLI. Upon first occurrence of GvL, longitudinal analyses revealed a preferential expansion of distinct CD8+ TRB clones (n=14). This did not occur in samples of patients without signs of GvL (n=11). Importantly, early repertoire changes 15 days after DLI predicted durable remission for the 36 months study follow-up. Furthermore, absence of clonal outgrowth of the CD8+ TRB repertoire after DLI was an early biomarker that predicted relapse at a median time of 11.2 months ahead of actual diagnosis. Additionally, unbiased sample analysis regardless of the clinical outcome revealed that patients with decreasing CD8+ TRB diversity at day 15 after DLI (n=13) had a lower relapse incidence (P=0.0040) compared to patients without clonal expansion (n=6). In conclusion, CD8+ TRB analysis may provide a reliable tool for predicting the efficacy of DLI and holds the potential to identify patients at risk for progression and relapse after DLI.

Depletion of CD25+ T cells inhibits CD8+ T cells clonal expansion and glioblastoma multiforme regression.

2008 ◽  
Vol 22 (S2) ◽  
pp. 514-514
Author(s):  
James F Curtin ◽  
Tamer M Fakhouri ◽  
Marianela Candolfi ◽  
Anderson Alden ◽  
Matthew R Edwards ◽  
...  
Keyword(s):  
T Cells ◽  
Glioblastoma Multiforme ◽  
Cd8 T Cells ◽  
Clonal Expansion

scholarly journals LTβR signaling in dendritic cells induces a type I IFN response that is required for optimal clonal expansion of CD8+T cells

2011 ◽  
Vol 108 (5) ◽  
pp. 2046-2051 ◽  
Author(s):  
Leslie Summers deLuca ◽  
Dennis Ng ◽  
Yunfei Gao ◽  
Michael E. Wortzman ◽  
Tania H. Watts ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Clonal Expansion ◽  
Type I ◽  
Type I Ifn

scholarly journals Stress and the anti-influenza immune response: Repeated social defeat augments clonal expansion of CD8+T cells during primary influenza A viral infection

2012 ◽  
Vol 243 (1-2) ◽  
pp. 34-42 ◽  
Author(s):  
Jacqueline W. Mays ◽  
Nicole D. Powell ◽  
John T. Hunzeker ◽  
Mark L. Hanke ◽  
Michael T. Bailey ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Viral Infection ◽  
Cd8 T Cells ◽  
Influenza A ◽  
Social Defeat ◽  
Clonal Expansion

Frequent occurrence ofin vivo clonal expansion of CD4− CD8− T cells bearing T cell receptor αβ chains in adult humans

1993 ◽  
Vol 23 (11) ◽  
pp. 2735-2739 ◽  
Author(s):  
Yoichiro Kusunoki ◽  
Yuko Hirai ◽  
Tomonori Hayashi ◽  
Seishi Kyoizumi ◽  
Keiko Takahashi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
Frequent Occurrence ◽  
Adult Humans
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