2. Academic Validation
  3. Layilin augments integrin activation to promote antitumor immunity

Layilin augments integrin activation to promote antitumor immunity

  • J Exp Med. 2020 Sep 7;217(9):e20192080. doi: 10.1084/jem.20192080.
Kelly M Mahuron 1,  Joshua M Moreau # 2,  Jeff E Glasgow 3,  Devi P Boda 2,  Mariela L Pauli 2,  Victoire Gouirand 2,  Luv Panjabi 2,  Robby Grewal 2,  Jacob M Luber 4 5,  Anubhav N Mathur 2 6,  Renny M Feldman 6,  Eric Shifrut 7,  Pooja Mehta 2,  Margaret M Lowe 2,  Michael D Alvarado 1,  Alexander Marson 7 8 9,  Meromit Singer 5 10 11,  Jim Wells 3,  Ray Jupp 6,  Adil I Daud 12,  Michael D Rosenblum 2
Affiliations

Affiliations

  • 1 Department of Surgery, University of California, San Francisco, San Francisco, CA.
  • 2 Department of Dermatology, University of California, San Francisco, San Francisco, CA.
  • 3 Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA.
  • 4 Department of Biomedical Informatics, Harvard Medical School, Boston, MA.
  • 5 Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA.
  • 6 T-REX Bio, Burlingame, CA.
  • 7 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA.
  • 8 Chan Zuckerberg Biohub, San Francisco, CA.
  • 9 Parker Institute for Cancer Immunotherapy, San Francisco, CA.
  • 10 Department of Immunology, Harvard Medical School, Boston, MA.
  • 11 Dana-Farber Cancer Institute, Boston, MA.
  • 12 Department of Medicine, University of California, San Francisco, San Francisco, CA.
  • # Contributed equally.
PMID: 32539073 DOI: 10.1084/jem.20192080
Abstract

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.

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