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 Feb 10;3(1):3-15.
doi: 10.4103/JIPO.JIPO_1_20. eCollection 2020 Feb.

Immune Checkpoint Blockade in Gastrointestinal Cancers: The Current Status and Emerging Paradigms

Mihailo Miljanic  1 , Anna Capasso  1 , Todd A Triplett  1 , S Gail Eckhardt  1 , Kyaw L Aung  1
Affiliations
Review

Immune Checkpoint Blockade in Gastrointestinal Cancers: The Current Status and Emerging Paradigms

Mihailo Miljanic et al. J Immunother Precis Oncol. .

Abstract

Immunotherapy is a rapidly evolving treatment paradigm that holds promise to provide long-lasting survival benefits for patients with cancer. This promise, however, remains unfulfilled for the majority of patients with gastrointestinal (GI) cancers, as significant limitations in efficacy exist with immune checkpoint inhibitors (ICIs) in this disease group. A plethora of novel combination treatment strategies are currently being investigated in various clinical trials to make them more efficacious as our understanding of molecular mechanisms mediating resistance to immunotherapy advances. In this article, we summarize the current status of immune checkpoint blockade in GI cancers and discuss the biological rationales that underlie the emerging treatment strategies being tested in ongoing clinical trials in combination with ICIs. We also highlight the promising early results from these strategies and provide future perspectives on enhancing response to immunotherapy for patients with GI cancers.

Keywords: Clinical trials; combination strategies; gastrointestinal cancers; immune checkpoint inhibitors; primary resistance.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest The authors disclosed no conflicts of interest related to this article.

Figures

Figure 1:
Figure 1:
Summary of key primary resistance mechanisms to immune checkpoint blockade and key strategies that are being employed to overcome the resistance in gastrointestinal cancers. EGFR: Epidermal growth factor receptor, MAPK: Mitogen activated protein kinase pathway, TAM: Tumor associated macrophages, TME: Tumor microenvironment.
See this image and copyright information in PMC

References

    1. GI Cancers Alliance. Available from: https://www.gicanceralliance.org [Accessed Sep 23, 2019]
    1. American Cancer Society. Available from: https://cancerstatisticscenter.cancer.org/#!/ [Accessed Sep 23, 2019]
    1. Rahib L, Smith BD, Aizenberg R et al. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21. - PubMed
    1. Albertini MR. The age of enlightenment in melanoma immunotherapy. J Immunother Cancer. 2018;6:80. - PMC - PubMed
    1. Karachaliou N, Fernandez-Bruno M, Rosell R. Strategies for first-line immunotherapy in squamous cell lung cancer: Are combinations a game changer? Transl Lung Cancer Res. 2018;7:S198–201. - PMC - PubMed

LinkOut - more resources