Understanding the effects of obesity on the immune profile of renal cell carcinoma (RCC) patients is critical, given the rising use of immunotherapies to treat advanced disease and recent reports of differential cancer immunotherapy outcomes with obesity. Here, we evaluated multiple immune parameters at the genetic, soluble protein, and cellular levels in peripheral blood and renal tumors from treatment-naive clear cell RCC (ccRCC) subjects (n = 69), to better understand the effects of host obesity (Body Mass Index "BMI" ≥ 30 kg/m2) in the absence of immunotherapy. Tumor-free donors (n = 38) with or without obesity were used as controls. In our ccRCC cohort, increasing BMI was associated with decreased percentages of circulating activated PD-1+CD8+ T cells, CD14+CD16neg classical monocytes, and Foxp3+ regulatory T cells (Tregs). Only CD14+CD16neg classical monocytes and Tregs were reduced when obesity was examined as a categorical variable. Obesity did not alter the percentages of circulating IFNγ+ CD8 T cells or IFNγ+, IL-4+, or IL-17A+ CD4 T cells in ccRCC subjects. Of 38 plasma proteins analyzed, six (CCL3, IL-1β, IL-1RA, IL-10, IL-17, and TNFα) were upregulated specifically in ccRCC subjects with obesity versus tumor-free controls with obesity. IGFBP-1 was uniquely decreased in ccRCC subjects with obesity versus non-obese ccRCC subjects. Immunogenetic profiling of ccRCC tumors revealed that 93% of examined genes were equivalently expressed and no changes in cell type scores were found in stage-matched tumors from obesity category II/III versus normal weight (BMI ≥ 35 kg/m2 versus 18.5-24.9 kg/m2, respectively) subjects. Intratumoral PLGF and VEGF-A proteins were elevated in ccRCC subjects with obesity. Thus, in ccRCC patients with localized disease, obesity is not associated with widespread detrimental alterations in systemic or intratumoral immune profiles. The effects of combined obesity and immunotherapy administration on immune parameters remains to be determined.
PloS one. 2020 May 29*** epublish ***
Justin T Gibson, Katlyn E Norris, Gal Wald, Claire M Buchta Rosean, Lewis J Thomas, Shannon K Boi, Laura A Bertrand, Megan Bing, Jennifer B Gordetsky, Jessy Deshane, Peng Li, James A Brown, Kenneth G Nepple, Lyse A Norian
Graduate Biomedical Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America., School of Health Professions Honors Undergraduate Research Program, University of Alabama at Birmingham, Birmingham, Alabama, United States of America., Department of Urology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America., Departments of Pathology and Urology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America., Department of Acute, Chronic, and Continuing Care, School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama, United States of America., Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.