Abstract
Since multiple front-line immune checkpoint inhibitor–based (ICI-based) combinations are approved for metastatic renal cell carcinoma, biomarkers predicting for ICI responses are needed past clinical prognostication scores and transcriptome gene expression profiling. Circulating markers represent opportunities to assess baseline and dynamic changes in immune cell frequency and cytokine levels while on treatment. We conducted an exploratory prospective correlative study of 33 patients with metastatic clear cell renal cell carcinoma undergoing treatment with ICIs and correlated changes in circulating immune cell subsets and cytokines with clinical responses to treatment. Cell frequencies and cytokine levels were compared between responders and nonresponders using unpaired parametric t tests, using prespecified alpha level of significance of 0.05. Classical monocyte subsets (CD14+CD16–), as well as 7 cytokines (IL-12/23 p40, macrophage inflammatory protein-1a, macrophage inflammatory protein-1b, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, IL-8, and TNF-α) were higher at baseline for responding versus nonresponding patients. Dynamic changes in thymus- and activation-regulated chemokine (TARC), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) also correlated with patients with ICI response. In summary, macrophage-activating agents were observed to be important in ICI response and may highlight the importance of the innate immune response in ICI responses.
Authors
Joyce Hwang, Eda Holl, Yuan Wu, Anika Agarwal, Mark D. Starr, Marco A. Reyes Martinez, Andrew Z. Wang, Andrew J. Armstrong, Michael R. Harrison, Daniel J. George, Andrew B. Nixon, Tian Zhang
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
