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The Potential of Combining Tubulin-Targeting Anticancer Therapeutics and Immune Therapy

Fong, Alexis, Durkin, Amanda, Lee, Hoyun·2019·International Journal of Molecular Sciences
DOI 10.3390/ijms20030586PMC PMC6387102
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Abstract

Cancer immune therapy has recently shown tremendous promise to combat many different cancers. The microtubule is a well-defined and very effective cancer therapeutic target. Interestingly, several lines of evidence now suggest that microtubules are intimately connected to the body’s immune responses. This raises the possibility that the combination of microtubule inhibitors and immune therapy can be a highly effective option for cancer treatments. However, our understanding on this potentially important aspect is still very limited, due in part to the multifaceted nature of microtubule functions. Microtubules are not only involved in maintaining cell morphology, but also a variety of cellular processes, including the movement of secretory vesicles and organelles, intracellular macromolecular assembly, signaling pathways, and cell division. Microtubule inhibitors may be subdivided into two classes: Anti-depolymerization agents such as the taxane family, and anti-polymerization agents such as colchicine and vinka alkaloids. These two different classes may have different effects on immune cell subtypes. Anti-depolymerization agents can not only induce NK cells, but also appear to inhibit T regulatory (Treg) cells. However, different inhibitors may have different functions even among the same class. For example, the doxetaxel anti-depolymerization agent up-regulates cytotoxic T cells, while paclitaxel down-regulates them. Certain anti-polymerization agents such as colchicine appear to down-regulate most immune cell types, while inducing dendritic cell maturation and increasing M1 macrophage population. In contrast, the vinblastine anti-polymerization agent activates many of these cell types, albeit down-regulating Treg cells. In this review, we focus on the various effects of tubulin inhibitors on the activities of the body’s immune system, in the hope of paving the way to develop an effective cancer therapy by combining tubulin-targeting anticancer agents and immune therapy.

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Figure 1 Demonstrates how the tubulin inhibitors affect the microtubules by preventing depolymerization or polymerization. Panel left illustrates the effects of paclitaxel and docetaxel (depolymerization inhibitors), while panel right illustrates the effects of colchicine and vinblastine (polymerization inhibitors).
Figure 1 Demonstrates how the tubulin inhibitors affect the microtubules by preventing depolymerization or polymerization. Panel left illustrates the effects of paclitaxel and docetaxel (depolymerization inhibitors), while panel right illustrates the effects of colchicine and vinblastine (polymerization inhibitors).CC BY · PubMed Central
Figure 2 Tubulin inhibitors and their effects on the various immune cell types. Green arrows indicate the ability of the drugs to induce activation and red arrows indicate the inhibition of that immune cell type.
Figure 2 Tubulin inhibitors and their effects on the various immune cell types. Green arrows indicate the ability of the drugs to induce activation and red arrows indicate the inhibition of that immune cell type.CC BY · PubMed Central

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Metadata

Authors
Fong, A., Durkin, A., & Lee, H.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2019-01-30
Volume
20
Issue
3
Pages
586
ISSN
1422-0067
DOI
10.3390/ijms20030586
PMC
PMC6387102
Cited by
50
References
3
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Northern Cancer Foundation (Not applicable)

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