Details

Autor(en) / Beteiligte

• Mahuron, Kelly M
• Moreau, Joshua M
• Glasgow, Jeff E
• Boda, Devi P
• Pauli, Mariela L
• Gouirand, Victoire
• Panjabi, Luv
• Grewal, Robby
• Luber, Jacob M
• Mathur, Anubhav N
• Feldman, Renny M
• Shifrut, Eric
• Mehta, Pooja
• Lowe, Margaret M
• Alvarado, Michael D
• Marson, Alexander
• Singer, Meromit
• Wells, Jim
• Jupp, Ray
• Daud, Adil I
• Rosenblum, Michael D

Titel

Layilin augments integrin activation to promote antitumor immunity

Ist Teil von

• The Journal of experimental medicine, 2020-09, Vol.217 (9)

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.