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 Ansell; Andrew L Feldman; James Cerhan; Anne Novak; Luis F Porrata; Svetomir Markovic; Brian K Link; Thomas E Witzig

doi:10.1002/ajh.24758

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

Journal article

Open access

Peer reviewed

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 Ansell, Andrew L Feldman, James Cerhan, Anne Novak, Luis F Porrata, Svetomir Markovic, Brian K Link, …

American journal of hematology, Vol.92(8), pp.752-758

08/2017

DOI: 10.1002/ajh.24758

PMID: 28383112

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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.

Adult

Aged

Aged, 80 and over

Biomarkers

Blood Cells - immunology

Blood Cells - metabolism

Combined Modality Therapy

Cytokines - blood

Female

Humans

Kaplan-Meier Estimate

Leukocyte Count

Lymphocytes - pathology

Lymphoma - diagnosis

Lymphoma - immunology

Lymphoma - metabolism

Lymphoma - therapy

Male

Middle Aged

Monocytes - pathology

Neoplasm Staging

Prognosis

Receptors, Interleukin-2 - metabolism

Young Adult

Details

Title: Subtitle: Associations between elevated pre-treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma
Creators: Moritz Binder - Department of Internal Medicine, Mayo Clinic , Rochester, Minnesota.
Megan M O'Byrne - Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
Matthew J Maurer - Mayo Clinic
Stephen Ansell - Mayo Clinic
Andrew L Feldman - Mayo Clinic
James Cerhan - Mayo Clinic in Florida
Anne Novak - Mayo Clinic
Luis F Porrata - Mayo Clinic
Svetomir Markovic - Mayo Clinic
Brian K Link - University of Iowa
Thomas E Witzig - Mayo Clinic
Resource Type: Journal article
Publication Details: American journal of hematology, Vol.92(8), pp.752-758
DOI: 10.1002/ajh.24758
PMID: 28383112
ISSN: 0361-8609
eISSN: 1096-8652
Grant note: DOI: 10.13039/100005189, name: Leukemia and Lymphoma Society
Language: English
Date published: 08/2017
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
Record Identifier: 9984359923402771

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