Harnessing tumorous flaws for immune supremacy: is miRNA-155 the weak link in breast cancer progression?
Samantha Sharma, … , Mateusz Opyrchal, Xiongbin Lu
Samantha Sharma, … , Mateusz Opyrchal, Xiongbin Lu
Published October 3, 2022
Citation Information: J Clin Invest. 2022;132(19):e163010. https://doi.org/10.1172/JCI163010.
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Commentary

Harnessing tumorous flaws for immune supremacy: is miRNA-155 the weak link in breast cancer progression?

Abstract

With the advent of immune checkpoint blockade (ICB) therapy, treatment strategies for late-stage cancers have seen a radical advancement. In this issue of the JCI, Wang et al. characterize the functional role of miR-155 in breast cancer and its potential in harnessing the efficacy of immunotherapy. The study reports that high expression levels of miR-155 in breast cancer cells downregulated suppressor of cytokine signaling 1 (SOCS1), increased the phosphorylated STAT1 (pSTAT1)/pSTAT3 ratio, and thereby stimulated chemoattractants for tumor infiltration of effector T cells. Moreover, miR-155 overexpression set the stage for ICB therapy via increased programmed death ligand 1 (PD-L1) expression on cancer cells and enhanced immunological memory response via the release of miR-155–containing extracellular vesicles. Collectively, these data suggest that miR-155 is a strong candidate as a prognostic biomarker for ICB therapy.

Authors

Samantha Sharma, Mateusz Opyrchal, Xiongbin Lu

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Figure 1

The role of miR-155 in breast cancer and its therapeutic translational potential.

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The role of miR-155 in breast cancer and its therapeutic translational p...
(A) Breast cancer patients with an elevated level of miR-155 (miR-155hi) have increased levels of tumor-infiltrating lymphocytes. (B) Mechanistically, tumor-associated miR-155 can upregulate chemokine production, specifically, CXCL9, CXCL10, CXCL11, and PD-L1 expression on the tumor cells. Furthermore, tumors expressing elevated levels of miR-155 release miR-155–enriched exosomes in the bloodstream. Overall, miR-155hi breast tumors have a better overall patient survival rate, elevated chemokine production, and an increase in tumor-infiltrating lymphocytes as compared with miR-155lo breast tumors. (C) At the clinical level, miR-155 and miR-155–enriched exosomes in liquid biopsy of patients can be used as positive prognostic markers for breast cancer. Further, therapeutic delivery of miR-155 may improve the effectiveness of ICB therapy via increased PD-L1 expression.