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Integrin CD11b activation drives anti-tumor innate immunity

Author

Listed:
  • 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
    University of California, San Diego)

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.

Suggested Citation

  • 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 Raja, 2018. "Integrin CD11b activation drives anti-tumor innate immunity," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07387-4
    DOI: 10.1038/s41467-018-07387-4
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    Cited by:

    1. Michael C. Schmid & Sang Won Kang & Hui Chen & Marc Paradise & Anghesom Ghebremedhin & Megan M. Kaneda & Shao-Ming Chin & Anh Do & D. Martin Watterson & Judith A. Varner, 2022. "PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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