Integrin αvβ8 on T cells suppresses anti-tumor immunity in multiple models and is a promising target for tumor immunotherapy

Cell Rep. 2021 Jul 6;36(1):109309. doi: 10.1016/j.celrep.2021.109309.


αvβ8 integrin, a key activator of transforming growth factor β (TGF-β), inhibits anti-tumor immunity. We show that a potent blocking monoclonal antibody against αvβ8 (ADWA-11) causes growth suppression or complete regression in syngeneic models of squamous cell carcinoma, mammary cancer, colon cancer, and prostate cancer, especially when combined with other immunomodulators or radiotherapy. αvβ8 is expressed at the highest levels in CD4+CD25+ T cells in tumors, and specific deletion of β8 from T cells is as effective as ADWA-11 in suppressing tumor growth. ADWA-11 increases expression of a suite of genes in tumor-infiltrating CD8+ T cells normally inhibited by TGF-β and involved in tumor cell killing, including granzyme B and interferon-γ. The in vitro cytotoxic effect of tumor CD8 T cells is inhibited by CD4+CD25+ cells, and this suppressive effect is blocked by ADWA-11. These findings solidify αvβ8 integrin as a promising target for cancer immunotherapy.

Keywords: CD8 T cells; TGFbeta; alphavbeta8; anti-tumor immunity; integrin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neoplasm / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CTLA-4 Antigen / immunology
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Granzymes / metabolism
  • Immunity*
  • Immunotherapy*
  • Integrins / metabolism*
  • Interferon-gamma / metabolism
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological*
  • Mutation / genetics
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Signal Transduction
  • Smad3 Protein / metabolism
  • Survival Analysis
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transforming Growth Factor beta / metabolism
  • Tumor Microenvironment / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism


  • Antibodies, Neoplasm
  • CTLA-4 Antigen
  • Integrins
  • Smad3 Protein
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • integrin alphavbeta8
  • Interferon-gamma
  • Granzymes