title: Prognostic value of regulatory T cells, lymphoma-associated macrophages, and MUM-1 expression in follicular lymphoma treated before and after the introduction of monoclonal antibody therapy: a Southwest Oncology Group Study.
abstract: BACKGROUND
  The purpose was to examine the prognostic impact of features of tumor cells and immune microenvironment in patients with follicular lymphoma treated with and without anti-CD20 monoclonal antibody therapy.
  
  
  METHODS
  Tissue microarrays were constructed from archived tissue obtained from patients on three sequential Southwest Oncology Group (SWOG) trials for FL. All three trials included anthracycline-based chemotherapy. Anti-CD20 monoclonal antibodies were included for patients in the latter two trials. Immunohistochemistry was used to study the number and distribution of cells staining for forkhead box protein P3 (FOXP3) and lymphoma-associated macrophages (LAMs) and the number of lymphoma cells staining for myeloma-associated antigen-1 (MUM-1). Cox proportional hazards regression was used to evaluate the association between marker expression and overall survival (OS).
  
  
  RESULTS
  The number or pattern of infiltrating FOXP3 cells and LAMs did not correlate with OS in sequential SWOG studies for FL. The presence of MUM-1 correlated with lower OS for patients who received monoclonal antibody but not for those treated with chemotherapy alone.
  
  
  CONCLUSIONS
  Immune cell composition of lymph nodes did not correlate with OS in this analysis of trials in FL. The mechanism of the observed correlation between MUM-1 expression and adverse prognosis in patients receiving monoclonal antibody therapy requires confirmation.
authors.affiliation: Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Cleveland. Electronic address: sweetej@ccf.org.
authors.forename: J W
authors.initials: JW
authors.lastname: Sweetenham
authors.affiliation: Southwest Oncology Group Statistical Center, Seattle.
authors.forename: B
authors.initials: B
authors.lastname: Goldman
authors.affiliation: Southwest Oncology Group Statistical Center, Seattle.
authors.forename: M L
authors.initials: ML
authors.lastname: LeBlanc
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic Foundation, Cleveland.
authors.forename: J R
authors.initials: JR
authors.lastname: Cook
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic Foundation, Cleveland.
authors.forename: R R
authors.initials: RR
authors.lastname: Tubbs
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle.
authors.forename: O W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle.
authors.forename: D G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Department of Medicine, University of Rochester Cancer, Rochester.
authors.forename: R I
authors.initials: RI
authors.lastname: Fisher
authors.affiliation: Department of Pathology, University of Arizona, Tucson.
authors.forename: L M
authors.initials: LM
authors.lastname: Rimsza
authors.affiliation: Department of Pathology, Oregon Health Sciences University, Portland, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Braziel
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic Foundation, Cleveland.
authors.forename: E D
authors.initials: ED
authors.lastname: Hsi
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001772:Blood Cell Count; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008495:Medical Oncology / Q000379:methods; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D015206:Southwestern United States; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D000911:Antibodies, Monoclonal; D050835:Interferon Regulatory Factors; D000099218:Interferon Regulatory Factor-4