Layilin augments integrin activation to promote antitumor immunity

J Exp Med. 2020 Sep 7;217(9):e20192080. doi: 10.1084/jem.20192080.


Tumor-infiltrating CD8+ T cells mediate antitumor immune responses. However, the mechanisms by which T cells remain poised to kill cancer cells despite expressing high levels of inhibitory receptors are unknown. Here, we report that layilin, a C-type lectin domain-containing membrane glycoprotein, is selectively expressed on highly activated, clonally expanded, but phenotypically exhausted CD8+ T cells in human melanoma. Lineage-specific deletion of layilin on murine CD8+ T cells reduced their accumulation in tumors and increased tumor growth in vivo. Congruently, gene editing of LAYN in human CD8+ T cells reduced direct tumor cell killing ex vivo. On a molecular level, layilin colocalized with integrin αLβ2 (LFA-1) on T cells, and cross-linking layilin promoted the activated state of this integrin. Accordingly, LAYN deletion resulted in attenuated LFA-1-dependent cellular adhesion. Collectively, our results identify layilin as part of a molecular pathway in which exhausted or "dysfunctional" CD8+ T cells enhance cellular adhesiveness to maintain their cytotoxic potential.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Carrier Proteins / metabolism*
  • Cell Adhesion
  • Cell Proliferation
  • Clone Cells
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic
  • Gene Editing
  • Humans
  • Immunity*
  • Integrins / metabolism*
  • Lectins, C-Type / metabolism*
  • Lymphocyte Activation / immunology
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma / immunology
  • Melanoma / pathology
  • Membrane Glycoproteins / metabolism*
  • Mice, Inbred C57BL
  • Neoplasm Metastasis
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Protein Binding
  • Talin / metabolism


  • Carrier Proteins
  • Cytokines
  • Integrins
  • LAYN protein, human
  • Lectins, C-Type
  • Lymphocyte Function-Associated Antigen-1
  • Membrane Glycoproteins
  • Talin
  • layilin protein, mouse