Obesity induces limited changes to systemic and local immune profiles in treatment-naive human clear cell renal cell carcinoma
PLOS ONE
Authors: Gibson, Justin T.; Norris, Katlyn E.; Wald, Gal; Rosean, Claire M. Buchta; Thomas, Lewis J.; Boi, Shannon K.; Bertrand, Laura A.; Bing, Megan; Gordetsky, Jennifer B.; Deshane, Jessy; Li, Peng; Brown, James A.; Nepple, Kenneth G.; Norian, Lyse A.
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/ m(2)) 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(+)CD16(neg) classical monocytes, and Foxp(3+) regulatory T cells (Tregs). Only CD14(+)CD16(neg) classical monocytes and Tregs were reduced when obesity was examined as a categorical variable. Obesity did not alter the percentages of circulating IFN gamma(+) CD8 T cells or IFN gamma(+), IL-4(+), or IL-17A(+) CD4 T cells in ccRCC subjects. Of 38 plasma proteins analyzed, six (CCL3, IL-1 beta, IL-12RA, 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 > 35 kg/m(2) versus 18.5-24.9 kg/m(2), 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.
Serum sCD14, PGLYRP2 and FGA as potential biomarkers for multidrug-resistant tuberculosis based on data-independent acquisition and targeted proteomics
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Authors: Chen, Jing; Han, Yu-Shuai; Yi, Wen-Jing; Huang, Huai; Li, Zhi-Bin; Shi, Li-Ying; Wei, Li-Liang; Yu, Yi; Jiang, Ting-Ting; Li, Ji-Cheng
Abstract
Multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis (TB) resistant to at least isoniazid and rifampicin, is a major concern of TB control worldwide. However, the diagnosis of MDR-TB remains a huge challenge to its prevention and control. To identify new diagnostic methods for MDR-TB, a mass spectrometry strategy of data-independent acquisition and parallel reaction monitoring was used to detect and validate differential serum proteins. The bioinformatic analysis showed that the functions of differential serum proteins between the MDR-TB group and the drug-sensitive tuberculosis group were significantly correlated to the complement coagulation cascade, surface adhesion and extracellular matrix receptor interaction, suggesting a disorder of coagulation in TB. Here, we identified three potential candidate biomarkers such as sCD14, PGLYRP2 and FGA, and established a diagnostic model using these three candidate biomarkers with a sensitivity of 81.2%, a specificity of 90% and the area under the curve value of 0.934 in receiver operation characteristics curve to diagnose MDR-TB. Our study has paved the way for a novel method to diagnose MDR-TB and may contribute to elucidate the mechanisms underlying MDR-TB.