Integrin CD11b activation drives anti-tumor innate immunity

Michael C. Schmid, Samia Q. Khan, Megan M. Kaneda, Paulina Pathria, Ryan Shepard, Tiani L. Louis, Sudarshan Anand, Gyunghwi Woo, Chris Leem, M. Hafeez Faridi, Terese Geraghty, Anugraha Rajagopalan, Seema Gupta, Mansoor Ahmed, Roberto I. Vazquez-Padron, David A. Cheresh, Vineet Gupta, Judith A. Varner

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11 Scopus citations

Abstract

Myeloid cells are recruited to damaged tissues where they can resolve infections and tumor growth or stimulate wound healing and tumor progression. Recruitment of these cells is regulated by integrins, a family of adhesion receptors that includes integrin CD11b. Here we report that, unexpectedly, integrin CD11b does not regulate myeloid cell recruitment to tumors but instead controls myeloid cell polarization and tumor growth. CD11b activation promotes pro-inflammatory macrophage polarization by stimulating expression of microRNA Let7a. In contrast, inhibition of CD11b prevents Let7a expression and induces cMyc expression, leading to immune suppressive macrophage polarization, vascular maturation, and accelerated tumor growth. Pharmacological activation of CD11b with a small molecule agonist, Leukadherin 1 (LA1), promotes pro-inflammatory macrophage polarization and suppresses tumor growth in animal models of murine and human cancer. These studies identify CD11b as negative regulator of immune suppression and a target for cancer immune therapy.

Original languageEnglish (US)
Article number5379
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Schmid, M. C., Khan, S. Q., Kaneda, M. M., Pathria, P., Shepard, R., Louis, T. L., Anand, S., Woo, G., Leem, C., Faridi, M. H., Geraghty, T., Rajagopalan, A., Gupta, S., Ahmed, M., Vazquez-Padron, R. I., Cheresh, D. A., Gupta, V., & Varner, J. A. (2018). Integrin CD11b activation drives anti-tumor innate immunity. Nature Communications, 9(1), [5379]. https://doi.org/10.1038/s41467-018-07387-4