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 () and Judith A. Varner ()
Additional contact information
Michael C. Schmid: University of California, San Diego
Samia Q. Khan: Rush University Medical Center
Megan M. Kaneda: University of California, San Diego
Paulina Pathria: University of California, San Diego
Ryan Shepard: University of California, San Diego
Tiani L. Louis: University of California, San Diego
Sudarshan Anand: University of California, San Diego
Gyunghwi Woo: University of California, San Diego
Chris Leem: University of California, San Diego
M. Hafeez Faridi: Rush University Medical Center
Terese Geraghty: Rush University Medical Center
Anugraha Rajagopalan: Rush University Medical Center
Seema Gupta: University of Miami Miller School of Medicine
Mansoor Ahmed: University of Miami Miller School of Medicine
Roberto I. Vazquez-Padron: University of Miami Leonard M. Miller School of Medicine
David A. Cheresh: University of California, San Diego
Vineet Gupta: Rush University Medical Center
Judith A. Varner: University of California, San Diego

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07387-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07387-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07387-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().