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Immunity. 2016 Jan 19;44(1):143-154. doi: 10.1016/j.immuni.2015.12.008. Epub 2016 Jan 12.

The PD-1 Axis Enforces an Anatomical Segregation of CTL Activity that Creates Tumor Niches after Allogeneic Hematopoietic Stem Cell Transplantation.

Author information

1
Dynamics of Immune Responses Unit, Equipe Labéllisée Ligue Contre le Cancer, Institut Pasteur, 75015 Paris, France; INSERM U668, rue du Dr Roux, 75015 Paris, France; Cellule Pasteur, University Paris Diderot, Sorbonne Paris Cité, 75015 Paris, France.
2
Dynamics of Immune Responses Unit, Equipe Labéllisée Ligue Contre le Cancer, Institut Pasteur, 75015 Paris, France; INSERM U668, rue du Dr Roux, 75015 Paris, France.
3
Dynamics of Immune Responses Unit, Equipe Labéllisée Ligue Contre le Cancer, Institut Pasteur, 75015 Paris, France; INSERM U668, rue du Dr Roux, 75015 Paris, France. Electronic address: philippe.bousso@pasteur.fr.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a curative treatment for hematologic malignancies, relies on donor cytotoxic T lymphocyte (CTL)-mediated graft-versus-leukemia (GVL) effect. Major complications of HSCT are graft-versus-host disease (GVHD) that targets specific tissues and tumor relapses. However, the mechanisms dictating the anatomical features of GVHD and GVL remain unclear. Here, we show that after HSCT, CTLs exhibited different killing activity in distinct tissues, being highest in the liver and lowest in lymph nodes. Differences were imposed by the microenvironment, partly through differential PD-1 ligand expression, which was strongly elevated in lymph nodes. Two-photon imaging revealed that PD-1 blockade restored CTL sensitivity to antigen and killing in lymph nodes. Weak CTL activity in lymph nodes promoted local tumor escape but could be reversed by anti-PD-1 treatment. Our results uncover a mechanism generating an anatomical segregation of CTL activity that might dictate sites of GVHD and create niches for tumor escape.

PMID:
26795248
DOI:
10.1016/j.immuni.2015.12.008
[Indexed for MEDLINE]
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