Journal article
Obesity induces limited changes to systemic and local immune profiles in treatment-naive human clear cell renal cell carcinoma
PloS one, Vol.15(5), pp.e0233795-e0233795
2020
DOI: 10.1371/journal.pone.0233795
PMCID: PMC7259552
PMID: 32469992
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 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.
Details
- Title: Subtitle
- Obesity induces limited changes to systemic and local immune profiles in treatment-naive human clear cell renal cell carcinoma
- Creators
- Justin T Gibson - University of Alabama at BirminghamKatlyn E Norris - University of Alabama at BirminghamGal Wald - Roy J. and Lucille A. Carver College of MedicineClaire M Buchta Rosean - Department of Urology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of AmericaLewis J Thomas - University of IowaShannon K Boi - University of Alabama at BirminghamLaura A Bertrand - Roy J. and Lucille A. Carver College of MedicineMegan Bing - Roy J. and Lucille A. Carver College of MedicineJennifer B Gordetsky - Vanderbilt University Medical CenterJessy Deshane - University of Alabama at BirminghamPeng Li - University of Alabama at BirminghamJames A Brown - University of IowaKenneth G Nepple - University of IowaLyse A Norian - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.15(5), pp.e0233795-e0233795
- DOI
- 10.1371/journal.pone.0233795
- PMID
- 32469992
- PMCID
- PMC7259552
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Grant note
- T32 GM008111 / NIGMS NIH HHS P30 DK079626 / NIDDK NIH HHS T32 AI007051 / NIAID NIH HHS R01 CA181088 / NCI NIH HHS P30 CA013148 / NCI NIH HHS P30 DK056336 / NIDDK NIH HHS
- Language
- English
- Date published
- 2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Urology
- Record Identifier
- 9984320074202771
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