Obesity induces limited changes to systemic and local immune profiles in treatment-naive human clear cell renal cell carcinoma

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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 IFNα+ CD8 T cells or IFNα+, IL-4+, or IL-17A+ CD4 T cells in ccRCC subjects. Of 38 plasma proteins analyzed, six (CCL3, IL-1ß, IL-1RA, IL-10, IL-17, and TNFa) 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 α 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.

Original languageEnglish
Article numbere0233795
JournalPloS one
Volume15
Issue number5
DOIs
StatePublished - May 2020

Fingerprint

Dive into the research topics of 'Obesity induces limited changes to systemic and local immune profiles in treatment-naive human clear cell renal cell carcinoma'. Together they form a unique fingerprint.

Cite this