Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality

Saha, Asim; O’Connor, Roddy S.; Thangavelu, Govindarajan; Lovitch, Scott B.; Dandamudi, Durga Bhavani; Wilson, Caleph B.; Vincent, Benjamin G.; Tkachev, Victor; Pawlicki, Jan M.; Furlan, Scott N.; Kean, Leslie S.; Aoyama, Kazutoshi; Taylor, Patricia A.; Panoskaltsis‐Mortari, Angela; Foncea, Rocı́o; Ranganathan, Parvathi; Devine, Steven M.; Burrill, Joel S.; Guo, Lili; Sacristán, Catarina; Snyder, Nathaniel W.; Blair, Ian A.; Milone, Michael C.; Dustin, Michael L.; Riley, James L.; Bernlohr, David A.; Murphy, William J.; Fife, Brian T.; Munn, David H.; Miller, Jeffrey S.; Serody, Jonathan S.; Freeman, Gordon J.; Sharpe, Arlene H.; Turka, Laurence A.; Blazar, Bruce R.

doi:10.1172/jci85796

Cited by 83 publications

(81 citation statements)

References 94 publications

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“…The data presented by Ni and colleagues demonstrate the importance of context-dependent function of PD-L1 in influencing donor CD8 + T cell responses during the process of GVL versus GVHD and reveal a critical role for CD4 + T cells in regulating these processes. A context-dependent function of PD-L1 was also recently described by Saha et al (24), who found that GVHD was reduced in mice receiving Pdl1 -/-donor cells but that the GVL response was maintained. Ni and colleagues added to this finding by demonstrating that PD-L1/CD80 interactions are critical to the GVL effect.…”

Section: Gvl Versus Gvhdsupporting

confidence: 63%

PD-L1 serves as a double agent in separating GVL from GVHD

Brennan¹,

Yang²

2017

Journal of Clinical Investigation

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Section: Gvl Versus Gvhdsupporting

confidence: 63%

PD-L1 serves as a double agent in separating GVL from GVHD

Brennan¹,

Yang²

2017

Journal of Clinical Investigation

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“…The role of multiple costimulatory pathways has been studied in acute GVHD including positive regulatory axes [CD28 54,55 , ICOS (CD278) 56 ], TNFR-superfamily receptors [CD40L(CD154), OX40(CD134), 4-1BB(CD137)] and negative regulatory pathways [CTLA-4(CD152) 55 , PD-1(CD279)/PD-L1(CD274) 57,58 and B7-H3 59 (CD276)], amongst others (Suppl. text, Suppl.…”

Section: T-cell Activation Co-stimulation Survival and Metabolism Imentioning

confidence: 99%

Acute Graft-versus-Host Disease — Biologic Process, Prevention, and Therapy

2017

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“…Furthermore, the second case suggests a direct mechanistic role of PD-1/PD-L1 interaction in the control of cGVHD, which has already been demonstrated in experimental models of acute GVHD [12][13][14][15]. Interestingly, PD-1 blockade has been reported to result in exacerbation of experimental cGVHD mediated by IL-17 + IFN-γ + T cells [16].…”

Section: Discussionmentioning

confidence: 65%

Potential Role of the PD-1/PD-L1 Axis in the Immune Regulation of Chronic GVHD

et al. 2017

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Background: Antibodies blocking the PD-1/PD-L1 axis have been shown to have substantial antitumor effects also in the treatment of Hodgkin's lymphoma (HL) relapsing after conventional chemotherapy or even autologous hematopoietic stem cell transplantation (autoHSCT). In the case of allogeneic HSCT (alloHSCT), this treatment bears the risk of inducing graft-versus-host disease (GVHD). So far, only a small number of patients who developed acute GVHD after PD-1 antibody administration are described in the literature. Case Reports: We herein report the cases of 2 HL patients after alloHSCT who both responded well to the therapy; however, 1 patient developed chronic GVHD (cGVHD) within 3 days of administration of nivolumab. This patient already had a history of cGVHD and interestingly showed manifestations at the very same sites. The other patient never showed any signs of cGVHD, even with the administration of 13 cycles of anti-PD-1 therapy and large doses of donor lymphocytes. Conclusion: The rapid reappearance of cGVHD after blockade of PD-1 implies an important role of PD-1/PD-L1 in peripheral immune tolerance in cGVHD after alloHSCT and warrants further investigation.

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Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality

Cited by 83 publications

References 94 publications

PD-L1 serves as a double agent in separating GVL from GVHD

PD-L1 serves as a double agent in separating GVL from GVHD

Acute Graft-versus-Host Disease — Biologic Process, Prevention, and Therapy

Potential Role of the PD-1/PD-L1 Axis in the Immune Regulation of Chronic GVHD

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