Associations between elevated pre-treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma

Moritz Binder, Megan M. O'Byrne, Matthew J. Maurer, Stephen Maxted Ansell, Andrew L Feldman, James R Cerhan, Anne J Novak, Luis F. Porrata, Svetomir Nenad Markovic, Brian K. Link, Thomas Elmer Witzig

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Abstract

Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n=390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r=-0.36), IL-12 (r=-0.17), IP-10 (r=-0.23), and MIG (r=-0.32) concentrations (p<0.001). Elevated IL-2R was independently associated with suppressed ALC (OR 2.69, 95% CI 1.77-4.07, p<0.001), elevated AMC (OR 2.05, 95% CI 1.34-3.14, p<0.001), and suppressed ALC/AMC ratios (OR 3.51, 95% CI 2.31-5.34, p<0.001). Both elevated IL-2R (HR 2.27, 95% CI 1.48-3.49, p<0.001) and suppressed ALC/AMC ratios (HR 1.53, 95% CI 1.03-2.28, p=0.037) were independently associated with inferior overall survival. These data support the notion that elevated serum cytokines are immunosuppressive and provide further rationale to target the tumor microenvironment for therapeutic benefit.

Original languageEnglish (US)
JournalAmerican Journal of Hematology
DOIs
StateAccepted/In press - 2017

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Immunosuppression
Monocytes
Lymphoma
Cytokines
Lymphocytes
Serum
Therapeutics
Tumor Microenvironment
T-Cell Lymphoma
Lymphocyte Count
Interleukin-12
Immunosuppressive Agents
Hodgkin Disease
B-Lymphocytes
Survival

ASJC Scopus subject areas

  • Hematology

Cite this

@article{5a111cd6eff147cd9d9f23ce45a477ee,
title = "Associations between elevated pre-treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma",
abstract = "Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n=390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r=-0.36), IL-12 (r=-0.17), IP-10 (r=-0.23), and MIG (r=-0.32) concentrations (p<0.001). Elevated IL-2R was independently associated with suppressed ALC (OR 2.69, 95{\%} CI 1.77-4.07, p<0.001), elevated AMC (OR 2.05, 95{\%} CI 1.34-3.14, p<0.001), and suppressed ALC/AMC ratios (OR 3.51, 95{\%} CI 2.31-5.34, p<0.001). Both elevated IL-2R (HR 2.27, 95{\%} CI 1.48-3.49, p<0.001) and suppressed ALC/AMC ratios (HR 1.53, 95{\%} CI 1.03-2.28, p=0.037) were independently associated with inferior overall survival. These data support the notion that elevated serum cytokines are immunosuppressive and provide further rationale to target the tumor microenvironment for therapeutic benefit.",
author = "Moritz Binder and O'Byrne, {Megan M.} and Maurer, {Matthew J.} and Ansell, {Stephen Maxted} and Feldman, {Andrew L} and Cerhan, {James R} and Novak, {Anne J} and Porrata, {Luis F.} and Markovic, {Svetomir Nenad} and Link, {Brian K.} and Witzig, {Thomas Elmer}",
year = "2017",
doi = "10.1002/ajh.24758",
language = "English (US)",
journal = "American Journal of Hematology",
issn = "0361-8609",
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TY - JOUR

T1 - Associations between elevated pre-treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma

AU - Binder, Moritz

AU - O'Byrne, Megan M.

AU - Maurer, Matthew J.

AU - Ansell, Stephen Maxted

AU - Feldman, Andrew L

AU - Cerhan, James R

AU - Novak, Anne J

AU - Porrata, Luis F.

AU - Markovic, Svetomir Nenad

AU - Link, Brian K.

AU - Witzig, Thomas Elmer

PY - 2017

Y1 - 2017

N2 - Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n=390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r=-0.36), IL-12 (r=-0.17), IP-10 (r=-0.23), and MIG (r=-0.32) concentrations (p<0.001). Elevated IL-2R was independently associated with suppressed ALC (OR 2.69, 95% CI 1.77-4.07, p<0.001), elevated AMC (OR 2.05, 95% CI 1.34-3.14, p<0.001), and suppressed ALC/AMC ratios (OR 3.51, 95% CI 2.31-5.34, p<0.001). Both elevated IL-2R (HR 2.27, 95% CI 1.48-3.49, p<0.001) and suppressed ALC/AMC ratios (HR 1.53, 95% CI 1.03-2.28, p=0.037) were independently associated with inferior overall survival. These data support the notion that elevated serum cytokines are immunosuppressive and provide further rationale to target the tumor microenvironment for therapeutic benefit.

AB - Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n=390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r=-0.36), IL-12 (r=-0.17), IP-10 (r=-0.23), and MIG (r=-0.32) concentrations (p<0.001). Elevated IL-2R was independently associated with suppressed ALC (OR 2.69, 95% CI 1.77-4.07, p<0.001), elevated AMC (OR 2.05, 95% CI 1.34-3.14, p<0.001), and suppressed ALC/AMC ratios (OR 3.51, 95% CI 2.31-5.34, p<0.001). Both elevated IL-2R (HR 2.27, 95% CI 1.48-3.49, p<0.001) and suppressed ALC/AMC ratios (HR 1.53, 95% CI 1.03-2.28, p=0.037) were independently associated with inferior overall survival. These data support the notion that elevated serum cytokines are immunosuppressive and provide further rationale to target the tumor microenvironment for therapeutic benefit.

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U2 - 10.1002/ajh.24758

DO - 10.1002/ajh.24758

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