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.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Moritz
authors.identifier: http://orcid.org/0000-0001-9014-9658
authors.initials: M
authors.lastname: Binder
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Megan M
authors.initials: MM
authors.lastname: O'Byrne
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ansell
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Feldman
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: James
authors.initials: J
authors.lastname: Cerhan
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Anne
authors.initials: A
authors.lastname: Novak
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Porrata
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Svetomir
authors.initials: S
authors.lastname: Markovic
authors.affiliation: Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Thomas E
authors.identifier: http://orcid.org/0000-0002-4215-6500
authors.initials: TE
authors.lastname: Witzig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001773:Blood Cells / Q000276:immunology* / Q000378:metabolism*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008214:Lymphocytes / Q000473:pathology; D008223:Lymphoma / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D015375:Receptors, Interleukin-2