TY - JOUR
T1 - SLAMF6 deficiency augments tumor killing and skews toward an effector phenotype revealing it as a novel T cell checkpoint
AU - Hajaj, Emma
AU - Eisenberg, Galit
AU - Klein, Shiri
AU - Frankenburg, Shoshana
AU - Merims, Sharon
AU - David, Inna Ben
AU - Eisenhaure, Thomas
AU - Henrickson, Sarah E.
AU - Villani, Alexandra Chloé
AU - Hacohen, Nir
AU - Abudi, Nathalie
AU - Abramovich, Rinat
AU - Cohen, Jonathan E.
AU - Peretz, Tamar
AU - Veillette, Andre
AU - Lotem, Michal
N1 - Publisher Copyright:
© Hajaj et al.
PY - 2020/3
Y1 - 2020/3
N2 - SLAMF6 is a homotypic receptor of the Ig-superfamily whose exact role in immune modulation has remained elusive. Its constitutive expression on resting and activated T cells precludes it from being a bona fide exhaustion marker. By breeding Pmel-1 mice with SLAMF6 -/- mice, we generated donors for T cells lacking SLAMF6 and expressing a transgenic TCR for gp100- melanoma antigen. Activated Pmel-1xSLAMF6 -/- CD8+ T cells displayed improved polyfunctionality and strong tumor cytolysis. T-bet was the dominant transcription factor in Pmel-1 x SLAMF6 -/- cells, and upon activation, they acquired an effector-memory phenotype. Adoptive transfer of Pmel-1 x SLAMF6 -/- T cells to melanoma-bearing mice resulted in lasting tumor regression in contrast to temporary responses achieved with Pmel-1 T cells. LAG-3 expression was elevated in the SLAMF6 -/- cells, and the addition of the LAG-3-blocking antibody to the adoptive transfer protocol improved the SLAMF6 -/- T cells and expedited the antitumor response even further. The results from this study support the notion that SLAMF6 is an inhibitory immune receptor whose absence enables powerful CD8+ T cells to eradicate tumors.
AB - SLAMF6 is a homotypic receptor of the Ig-superfamily whose exact role in immune modulation has remained elusive. Its constitutive expression on resting and activated T cells precludes it from being a bona fide exhaustion marker. By breeding Pmel-1 mice with SLAMF6 -/- mice, we generated donors for T cells lacking SLAMF6 and expressing a transgenic TCR for gp100- melanoma antigen. Activated Pmel-1xSLAMF6 -/- CD8+ T cells displayed improved polyfunctionality and strong tumor cytolysis. T-bet was the dominant transcription factor in Pmel-1 x SLAMF6 -/- cells, and upon activation, they acquired an effector-memory phenotype. Adoptive transfer of Pmel-1 x SLAMF6 -/- T cells to melanoma-bearing mice resulted in lasting tumor regression in contrast to temporary responses achieved with Pmel-1 T cells. LAG-3 expression was elevated in the SLAMF6 -/- cells, and the addition of the LAG-3-blocking antibody to the adoptive transfer protocol improved the SLAMF6 -/- T cells and expedited the antitumor response even further. The results from this study support the notion that SLAMF6 is an inhibitory immune receptor whose absence enables powerful CD8+ T cells to eradicate tumors.
UR - http://www.scopus.com/inward/record.url?scp=85082092774&partnerID=8YFLogxK
U2 - 10.7554/eLife.52539
DO - 10.7554/eLife.52539
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C2 - 32122464
AN - SCOPUS:85082092774
VL - 9
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e52539
ER -