Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jan 28;21(3):838.
doi: 10.3390/ijms21030838.

Mass Spectrometry-Based Multivariate Proteomic Tests for Prediction of Outcomes on Immune Checkpoint Blockade Therapy: The Modern Analytical Approach

Julia Grigorieva  1 , Senait Asmellash  1 , Lelia Net  1 , Maxim Tsypin  1 , Heinrich Roder  1 , Joanna Roder  1
Affiliations
Review

Mass Spectrometry-Based Multivariate Proteomic Tests for Prediction of Outcomes on Immune Checkpoint Blockade Therapy: The Modern Analytical Approach

Julia Grigorieva et al. Int J Mol Sci. .

Abstract

The remarkable success of immune checkpoint inhibitors (ICIs) has given hope of cure for some patients with advanced cancer; however, the fraction of responding patients is 15-35%, depending on tumor type, and the proportion of durable responses is even smaller. Identification of biomarkers with strong predictive potential remains a priority. Until now most of the efforts were focused on biomarkers associated with the assumed mechanism of action of ICIs, such as levels of expression of programmed death-ligand 1 (PD-L1) and mutation load in tumor tissue, as a proxy of immunogenicity; however, their performance is unsatisfactory. Several assays designed to capture the complexity of the disease by measuring the immune response in tumor microenvironment show promise but still need validation in independent studies. The circulating proteome contains an additional layer of information characterizing tumor-host interactions that can be integrated into multivariate tests using modern machine learning techniques. Here we describe several validated serum-based proteomic tests and their utility in the context of ICIs. We discuss test performances, demonstrate their independence from currently used biomarkers, and discuss various aspects of associated biological mechanisms. We propose that serum-based multivariate proteomic tests add a missing piece to the puzzle of predicting benefit from ICIs.

Keywords: Biomarkers; circulating proteome; immune checkpoint inhibitors; mass spectrometry; multivariate tests.

PubMed Disclaimer

Conflict of interest statement

Senait Asmellash, Joanna Roder, Lelia Net, and Heinrich Roder are employees of Biodesix, Inc and hold stock options therein. Joanna Roder, Julia Grigorieva, Maxim Tsypin, Senait Asmellash, and Heinrich Roder are inventors on related patents or patent applications assigned to Biodesix, Inc.

Figures

Figure 1
Figure 1
OS by pairwise test classifications in the lung cancer development set by ICB and PIR (A), BDX008 and PIR (B), and BDX008 and ICB (C). Sens = Sensitive; Res = Resistant; NotRes = Not Resistant; mOS = median OS; m = months.
Figure 1
Figure 1
OS by pairwise test classifications in the lung cancer development set by ICB and PIR (A), BDX008 and PIR (B), and BDX008 and ICB (C). Sens = Sensitive; Res = Resistant; NotRes = Not Resistant; mOS = median OS; m = months.
Figure 2
Figure 2
Kaplan–Meier plots of outcome data by BDX008 classification for patients in defined by neutrophil-to-lymphocyte ratio (NLR).
See this image and copyright information in PMC

References

    1. Topalian S.L., Hodi F.S., Brahmer J.R., Gettinger S.N., Smith D.C., McDermott D.F., Powderly J.D., Sosman J.A., Atkins M.B., Leming P.D., et al. Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non–Small Cell Lung Cancer Treated With Nivolumab. JAMA Oncol. 2019;5:1411–1420. doi: 10.1001/jamaoncol.2019.2187. - DOI - PMC - PubMed
    1. Zimmermann S., Peters S. Appraising the Tail of the Survival Curve in the Era of PD-1/PD-L1 Checkpoint Blockade Editorial. JAMA Oncol. 2019;5:1403–1405. doi: 10.1001/jamaoncol.2019.2186. [Epub ahead of print] - DOI - PubMed
    1. Music M., Prassas I., Diamandis E.P. Optimizing cancer immunotherapy: Is it time for personalized predictive biomarkers? Crit. Rev. Clin. Lab. Sci. 2018;55:466–479. doi: 10.1080/10408363.2018.1499706. - DOI - PubMed
    1. Pitteri S.J., Kelly-Spratt K.S., Gurley K.E., Kennedy J., Buson T.B., Chin A., Wang H., Zhang Q., Wong C.H., Chodosh L.A., et al. Tumor Microenvironment-Derived Proteins Dominate the Plasma Proteome Response during Breast Cancer Induction and Progression. Cancer Res. 2011;71:5090–5100. doi: 10.1158/0008-5472.CAN-11-0568. - DOI - PMC - PubMed
    1. Subramanian A., Tamayo P., Mootha V.K., Mukherjee S., Ebert B.L., Gillette M.A., Paulovich A., Pomeroy S.L., Golub T.R., Lander E.S., et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA. 2005;102:15545–15550. doi: 10.1073/pnas.0506580102. - DOI - PMC - PubMed