TY - JOUR
T1 - Immune dysregulation in cancer patients developing immune-related adverse events
AU - Khan, Shaheen
AU - Khan, Saad
AU - Luo, Xin
AU - Fattah, Farjana J.
AU - Saltarski, Jessica
AU - Gloria-McCutchen, Yvonne
AU - Lu, Rong
AU - Xie, Yang
AU - Li, Quan
AU - Wakeland, Edward K
AU - Gerber, David E
N1 - Funding Information:
Funding: This study was given in part by a National Cancer Institute (NCI) Midcareer Investigator Award in Patient-Oriented Research (K24 CA201543-01 to D.E.G.), the David M.Crowley Foundation, the Peter Bradley Carlson Trust, the University of Texas Lung Cancer Specialized Program in Research Excellence (SPORE, P50-CA-070907-08S1 to D.E.G.) and the Cancer Prevention and Research Institute of Texas (CPRIT, RP15096), the Edwin L. Cox Distinguished Chair, the Human Genomics/Microarray Core and the Biomarker Research Core and Biostatistics Shared Resources at the Harold C.Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, which is supported in part by NCI Cancer Center Support Grant 1P30 CA142543-01.
Publisher Copyright:
© 2018, Cancer Research UK.
PY - 2019/1/8
Y1 - 2019/1/8
N2 - Background: Up to 40% of cancer patients on immune checkpoint inhibitors develop clinically significant immune-related adverse events (irAEs). The role of host immune status and function in predisposing patients to the development of irAEs remains unknown. Methods: Sera from 65 patients receiving immune checkpoint inhibitors and 13 healthy controls were evaluated for 40 cytokines at pre-treatment, after 2–3 weeks and after 6 weeks and analysed for correlation with the development of irAEs. Results: Of the 65 cancer patients enrolled, 55% were women; the mean age was 65 years and 98% received anti-PD1/PDL1 therapy. irAEs occurred in 35% of cases. Among healthy controls, cytokine levels were stable over time and lower than those in cancer patients at baseline. Significant increases in CXCL9, CXCL10, CXCL11 and CXCL13 occurred 2 weeks post treatment, and in CXCL9, CXCL10, CXCL11, CXCL13, IL-10 and CCL26 at 6 weeks post treatment. Patients who developed irAEs had lower levels of CXCL9, CXCL10, CXCL11 and CXCL19 at baseline and exhibited greater increases in CXCL9 and CXCL10 levels at post treatment compared to patients without irAEs. Conclusions: Patients who developed irAEs have lower baseline levels and greater post-treatment increases in multiple cytokine levels, suggesting that underlying immune dysregulation may be associated with heightened risk for irAEs.
AB - Background: Up to 40% of cancer patients on immune checkpoint inhibitors develop clinically significant immune-related adverse events (irAEs). The role of host immune status and function in predisposing patients to the development of irAEs remains unknown. Methods: Sera from 65 patients receiving immune checkpoint inhibitors and 13 healthy controls were evaluated for 40 cytokines at pre-treatment, after 2–3 weeks and after 6 weeks and analysed for correlation with the development of irAEs. Results: Of the 65 cancer patients enrolled, 55% were women; the mean age was 65 years and 98% received anti-PD1/PDL1 therapy. irAEs occurred in 35% of cases. Among healthy controls, cytokine levels were stable over time and lower than those in cancer patients at baseline. Significant increases in CXCL9, CXCL10, CXCL11 and CXCL13 occurred 2 weeks post treatment, and in CXCL9, CXCL10, CXCL11, CXCL13, IL-10 and CCL26 at 6 weeks post treatment. Patients who developed irAEs had lower levels of CXCL9, CXCL10, CXCL11 and CXCL19 at baseline and exhibited greater increases in CXCL9 and CXCL10 levels at post treatment compared to patients without irAEs. Conclusions: Patients who developed irAEs have lower baseline levels and greater post-treatment increases in multiple cytokine levels, suggesting that underlying immune dysregulation may be associated with heightened risk for irAEs.
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U2 - 10.1038/s41416-018-0155-1
DO - 10.1038/s41416-018-0155-1
M3 - Article
C2 - 30377338
AN - SCOPUS:85055747147
SN - 0007-0920
VL - 120
SP - 63
EP - 68
JO - British journal of cancer
JF - British journal of cancer
IS - 1
ER -