| First Author | Mahuron KM | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 9 | PubMed ID | 32539073 |
| Mgi Jnum | J:302853 | Mgi Id | MGI:6510650 |
| Doi | 10.1084/jem.20192080 | Citation | Mahuron KM, et al. (2020) Layilin augments integrin activation to promote antitumor immunity. J Exp Med 217(9) |
| abstractText | 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 alphaLbeta2 (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. |
