[HTML][HTML] Immune dysregulation in cancer patients developing immune-related adverse events

S Khan, SA Khan, X Luo, FJ Fattah, J Saltarski… - British journal of …, 2019 - nature.com
S Khan, SA Khan, X Luo, FJ Fattah, J Saltarski, Y Gloria-McCutchen, R Lu, Y Xie, Q Li…
British journal of cancer, 2019nature.com
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 …
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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