title: The Relationship between Obesity, Prostate Tumor Infiltrating Lymphocytes and Macrophages, and Biochemical Failure.
abstract: BACKGROUND
  Obesity reflects a chronic inflammatory environment that may contribute to prostate cancer progression and poor treatment outcomes. However, it is not clear which mechanisms drive this association within the tumor microenvironment. The aim of this pilot study was to examine prostatic inflammation via tumor infiltrating lymphocytes and macrophages characterized by obesity and cancer severity.
  
  
  METHODS
  We studied paraffin-embedded prostatectomy tissue from 99 participants (63 non-obese and 36 obese) from the Study of Clinical Outcomes, Risk and Ethnicity (University of Pennsylvania). Pathologists analyzed the tissue for type and count of lymphocytes and macrophages, including CD3, CD8, FOXP3, and CD68. Pathology data were linked to clinical and demographic variables. Statistical analyses included frequency tables, Kruskal-Wallis tests, Spearman correlations, and multivariable models.
  
  
  RESULTS
  We observed positive univariate associations between the number of CD68 cells and tumor grade (p = 0.019). In multivariable analysis, CD8 counts were associated with time to biochemical failure (HR = 1.09, 95% CI = 1.004-1.192, p-value = 0.041.) There were no differences in lymphocytes or macrophages by obesity status or BMI.
  
  
  CONCLUSIONS
  The number of lymphocytes and macrophages in the tumor microenvironment did not differ by obesity status. However, these inflammation markers were associated with poor prostate cancer outcomes. Further examination of underlying mechanisms that influence obesity-related effects on prostate cancer outcomes is warranted. Such research will guide immunotherapy protocols and weight management as they apply to diverse patient populations and phenotypes.
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Charnita
authors.initials: C
authors.lastname: Zeigler-Johnson
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Knashawn H
authors.initials: KH
authors.lastname: Morales
authors.affiliation: Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Priti
authors.initials: P
authors.lastname: Lal
authors.affiliation: Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Feldman
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D016896:Treatment Outcome; D059016:Tumor Microenvironment; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D017252:CD3 Complex; D016827:CD8 Antigens; D051858:Forkhead Transcription Factors; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C418974:FOXP3 protein, human