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
. 2018 Oct;13(5):383-395.
doi: 10.1007/s11899-018-0471-9.

Strategies for Predicting Response to Checkpoint Inhibitors

Roberta Zappasodi  1   2 , Jedd D Wolchok  1   2   3   4 , Taha Merghoub  5   6   7
Affiliations
Review

Strategies for Predicting Response to Checkpoint Inhibitors

Roberta Zappasodi et al. Curr Hematol Malig Rep. 2018 Oct.

Erratum in

Abstract

Purpose of review: Despite the clinical successes of immune checkpoint blockade across multiple tumor types, many patients do not respond to these therapies or become resistant after an initial response. This underscores the need to improve our understanding of the molecular determinants of response to guide more personalized and rational utilization of these therapies. Here, we describe available biomarkers of checkpoint blockade activity by classifying them into four major categories: tumor-intrinsic, immune microenvironmental, host-related, and dynamic factors.

Recent findings: The clinical experience accumulated thus far with checkpoint blockade now offers the opportunity to comprehensively study the molecular and immune features associated with response. This is yielding a growing set of biomarkers whose integration will be key to more accurately predict clinical outcome. We propose a model for systematic assessment of available baseline and dynamic biomarkers in relationship with patients' outcomes. This will improve our understanding of the tumor-immune interactions and dynamics that predict a clinical response and will provide key information to develop more personalized and effective treatment strategies.

Keywords: Gut microbiota; Immune checkpoint; Immunotherapy; Neoantigens; Response biomarkers; T cells.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Immunograms of baseline and dynamic biomarkers. Examples of immunograms, including available baseline and dynamic biomarkers, potentially associated with response or lack of response to immune checkpoint blockade (ICB). Systematic assessment of biomarker immunograms before and after treatment in correlation with outcome will help define the tumor-immune state(s) and type of evolution that predict a clinical response
See this image and copyright information in PMC

References

    1. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–6. - PubMed
    1. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800. - PubMed
    1. Zappasodi R, Merghoub T, Wolchok JD. Emerging concepts for immune checkpoint blockade-based combination therapies. Cancer Cell. 2018;33(4):581–98. - PMC - PubMed
    1. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. - PMC - PubMed

    1. Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26.

      •• This trial together with the one reported in ref 4 demonstrated the clinical benefit of ipilimumab in metastatic melanoma patients and led to the FDA approval of ipilimumab in 2011.

Publication types