The Relationship between Obesity, Prostate Tumor Infiltrating Lymphocytes and Macrophages, and Biochemical Failure

• Published in: PloS one 2016-08, Vol.11 (8), p.e0159109-e0159109
• Main Authors: Zeigler-Johnson, Charnita, Morales, Knashawn H, Lal, Priti, Feldman, Michael
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Biology and Life Sciences; Biomarkers, Tumor - metabolism; Body mass; Breast cancer; Cancer; Cancer research; Cancer surgery; Cancer treatment; CD3 antigen; CD3 Complex - metabolism; CD8 antigen; CD8 Antigens - metabolism; Demographic variables; Demographics; Development and progression; Failure analysis; Forkhead Transcription Factors - metabolism; Foxp3 protein; Humans; Immunotherapy; Inflammation; Lymphocytes; Lymphocytes, Tumor-Infiltrating - metabolism; Macrophages; Macrophages - metabolism; Male; Medical records; Medicine and Health Sciences; Middle Aged; Minority & ethnic groups; Obesity; Obesity - immunology; Obesity - metabolism; Paraffin; Pathology; Pilot Projects; Prostate; Prostate cancer; Prostatectomy; Prostatic Neoplasms - immunology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - therapy; Statistical analysis; Studies; Treatment Outcome; Tumor Microenvironment; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0159109

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. 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. 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. 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.