Programmed death ligand 1 (PD-L1) expression influences the immune-tolerogenic microenvironment in antiretroviral therapy-refractory Kaposi's sarcoma: a pilot study

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Title: Programmed death ligand 1 (PD-L1) expression influences the immune-tolerogenic microenvironment in antiretroviral therapy-refractory Kaposi's sarcoma: a pilot study
Author(s): Mletzko, S
Pinato, DJ
Robey, RC
Pria, AD
Benson, P
Imami, N
Bower, M
Item Type: Journal Article
Abstract: Upregulation of programmed death ligand 1 (PD-L1) is a mechanism of immune escape utilized by a variety of tumors. PD-L1 expression in tumor cells or in the surrounding infiltrate correlates with clinical responsiveness to novel therapies targeting the PD-1/PD-L1 immune checkpoint. In the context of HIV-1 infection, Kaposi's sarcoma (KS) is largely responsive to restoration of immunity following combination antiretroviral therapy (cART), but there is a subset that is not. We hypothesized that this subset of cART-refractory KS may utilize the PD-L1 pathway of immune escape. We found that PD-L1 expressing KS had a denser CD8+ T cell (p = 0.03) and PD-L1 positive macrophage peritumoral infiltrate (p = 0.04) to suggest the involvement of PD-L1 in shaping an immune-tolerogenic microenvironment in cART-refractory KS. The presence of PD-L1 expression in association with immune-infiltrating cells provides rationale for the clinical development PD-1/PD-L1-targeted checkpoint inhibitors in cART-refractory KS.
Publication Date: 7-Apr-2017
Date of Acceptance: 7-Apr-2017
URI: http://hdl.handle.net/10044/1/53248
DOI: https://dx.doi.org/10.1080/2162402X.2017.1304337
ISSN: 2162-4011
Publisher: Taylor & Francis
Journal / Book Title: OncoImmunology
Volume: 6
Issue: 8
Copyright Statement: This is an Accepted Manuscript of an article published by Taylor & Francis Group in OncoImmunology on 7 Apr 2017, available online at: http://www.tandfonline.com/10.1080/2162402X.2017.1304337
Sponsor/Funder: Chelsea & Westminster Health Charity
ViiV Healthcare UK Limited
St Stephen's Aids Trust
Funder's Grant Number: JRC FS 002 03/13-14
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Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Immunology
cART
HIV
KS
microenvironment
PD-L1
CD8 T-CELLS
B7 FAMILY
CANCER
INTERLEUKIN-10
MALIGNANCIES
INFECTION
ANTIBODY
SAFETY
MEMBER
B7-H1
HIV
KS
PD-L1
cART
microenvironment
Publication Status: Published
Article Number: e1304337
Appears in Collections:Division of Surgery
Division of Cancer
Department of Medicine
Faculty of Medicine



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