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Comment
. 2019 Dec 2;129(12):5089-5091.
doi: 10.1172/JCI133415.

Cancer immunotherapy needs to learn how to stick to its guns

Asmi Chakraborty, Charles J Dimitroff
Comment

Cancer immunotherapy needs to learn how to stick to its guns

Asmi Chakraborty et al. J Clin Invest. .

Abstract

Cancer immunotherapy and its budding effectiveness at improving patient outcomes has revitalized our hope to fight cancer in a logical and safe manner. Immunotherapeutic approaches to reengage the immune system have largely focused on reversing immune checkpoint inhibitor pathways, which suppress the antitumor response. Although these approaches have generated much excitement, they still lack absolute success. Interestingly, newly described host-tumor sugar chains (glycosylations) and glycosylation-binding proteins (lectins) play key roles in evading the immune system to determine cancer progression. In this issue of the JCI, Nambiar et al. used patient head and neck tumors and a mouse model system to investigate the role of galactose-binding lectin 1 (Gal1) in immunotherapy resistance. The authors demonstrated that Gal1 can affect immune checkpoint inhibitor therapy by increasing immune checkpoint molecules and immunosuppressive signaling in the tumor. Notably, these results suggest that targeting a tumor's glycobiological state will improve treatment efficacy.

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Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1. Galectin inhibitors enhance tumor immune surveillance.
(A) Gal1 secreted by tumor cells primes the endothelial cells to express PD-L1 and Gal9, both of which lead to T cell anergy as well as reduced T cell infiltration. T cells are also directly targeted by Gal1 to induce an immune-suppressive phenotype as well as apoptosis. (B) Treatment with a Gal1 inhibitor increases T cell infiltration. (C) Treatment with a Gal1 inhibitor in combination with immune checkpoint inhibitors enhances immune surveillance, with increased infiltration of T cells.
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