title: Serum CD163 and TARC as disease response biomarkers in classical Hodgkin lymphoma.
abstract: OBJECTIVE
  Candidate circulating disease response biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin-Reed-Sternberg (HRS) cells or nonmalignant tumor-infiltrating cells. HRS cells are sparse within the diseased node, whereas benign CD163(+) M2 tissue-associated macrophages (TAM) are prominent. CD163(+) cells within the malignant node may be prognostic, but there is no data on serum CD163 (sCD163). The HRS-specific serum protein sTARC shows promise as a disease response biomarker. Tumor-specific and tumor-infiltrating circulating biomarkers have not been compared previously.
  
  
  METHODS
  We prospectively measured sCD163 and sTARC in 221 samples from 47 patients with Hodgkin lymphoma and 21 healthy participants. Blood was taken at five fixed time-points prior, during, and after first-line therapy. Results were compared with radiological assessment and plasma Epstein-Barr virus DNA (EBV-DNA). Potential sources of circulating CD163 were investigated, along with immunosuppressive properties of CD163.
  
  
  RESULTS
  Pretherapy, both sCD163 and sTARC were markedly elevated compared with healthy and complete remission samples. sCD163 better reflected tumor burden during therapy, whereas sTARC had greater value upon completion of therapy. sCD163 correlated with plasma EBV-DNA, and associated with B symptoms, stage, and lymphopenia. Circulating CD163(+) monocytes were elevated in patients, indicating that sCD163 are likely derived from circulating and intratumoral cells. Depletion of cHL CD163(+) monocytes markedly enhanced T-cell proliferation, implicating monocytes and/or TAMs as potential novel targets for immunotherapeutic manipulation.
  
  
  CONCLUSIONS
  The combination of circulating tumor-infiltrate (sCD163) and tumor-specific (sTARC) proteins is more informative than either marker alone as disease response biomarkers in early and advanced disease during first-line therapy for cHL.
authors.affiliation: Clinical Immunohaematology Laboratory, Queensland Institute of Medical Research (QIMR), Queensland, Australia.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Jones
authors.forename: Frank
authors.initials: F
authors.lastname: Vari
authors.forename: Colm
authors.initials: C
authors.lastname: Keane
authors.forename: Pauline
authors.initials: P
authors.lastname: Crooks
authors.forename: Jamie P
authors.initials: JP
authors.lastname: Nourse
authors.forename: Louise A
authors.initials: LA
authors.lastname: Seymour
authors.forename: David
authors.initials: D
authors.lastname: Gottlieb
authors.forename: David
authors.initials: D
authors.lastname: Ritchie
authors.forename: Devinder
authors.initials: D
authors.lastname: Gill
authors.forename: Maher K
authors.initials: MK
authors.lastname: Gandhi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D054414:Chemokine CCL17 / Q000097:blood*; D005260:Female; D006689:Hodgkin Disease / Q000097:blood* / Q000276:immunology / Q000473:pathology; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D054414:Chemokine CCL17; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface