Immune dysregulation in cancer patients developing immune-related adverse events

Shaheen Khan, Saad Khan, Xin Luo, Farjana J. Fattah, Jessica Saltarski, Yvonne Gloria-McCutchen, Rong Lu, Yang Xie, Quan Li, Edward K Wakeland, David E Gerber

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalBritish Journal of Cancer
DOIs
StateAccepted/In press - Jan 1 2018

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Neoplasms
Cytokines
Therapeutics
Interleukin-10
Serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Immune dysregulation in cancer patients developing immune-related adverse events. / Khan, Shaheen; Khan, Saad; Luo, Xin; Fattah, Farjana J.; Saltarski, Jessica; Gloria-McCutchen, Yvonne; Lu, Rong; Xie, Yang; Li, Quan; Wakeland, Edward K; Gerber, David E.

In: British Journal of Cancer, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "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.",
author = "Shaheen Khan and Saad Khan and Xin Luo and Fattah, {Farjana J.} and Jessica Saltarski and Yvonne Gloria-McCutchen and Rong Lu and Yang Xie and Quan Li and Wakeland, {Edward K} and Gerber, {David E}",
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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

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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.

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