2017
DOI: 10.1080/2162402x.2017.1304337
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Programmed death ligand 1 (PD-L1) expression influences the immune-tolerogenic microenvironment in antiretroviral therapy-refractory Kaposi's sarcoma: A pilot study

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 cA… Show more

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Cited by 15 publications
(23 citation statements)
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“…Other novel therapeutic approaches being studied for treating other neoplasms — in particular, the blockade of inhibitory receptors (for example, programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) and cytotoxic T lymphocyte protein 4 (CTLA4)) that might otherwise prevent effective immune responses to virally induced neoplasms 236 — are being explored in KS. Indeed, PDL1 and PD1 are expressed in HIV-positive KS tissue samples 237 , including samples derived from patients on cART with well-controlled HIV and high CD4 cell counts 238 . Pilot studies of the use of immune checkpoint inhibitors in KS have been promising both in patients with HIV 239 and in patients who are HIV seronegative 240 .…”
Section: Discussionmentioning
confidence: 99%
“…Other novel therapeutic approaches being studied for treating other neoplasms — in particular, the blockade of inhibitory receptors (for example, programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) and cytotoxic T lymphocyte protein 4 (CTLA4)) that might otherwise prevent effective immune responses to virally induced neoplasms 236 — are being explored in KS. Indeed, PDL1 and PD1 are expressed in HIV-positive KS tissue samples 237 , including samples derived from patients on cART with well-controlled HIV and high CD4 cell counts 238 . Pilot studies of the use of immune checkpoint inhibitors in KS have been promising both in patients with HIV 239 and in patients who are HIV seronegative 240 .…”
Section: Discussionmentioning
confidence: 99%
“…The ligation of PD-1 and PD-L1 or PD-L2 on tumor cells or antigenpresenting cells (APCs) elicits an immunosuppressive response, which implements subsequent metabolic reprogramming in T cells, decreases effector T cells and memory T cells, and increases Treg and exhausted T cell abundance (10). For the past few years, the abundance of PD-L1 protein in the HNSCC tumor, with its microenvironment sphere, has been the focus of numerous studies (2,(11)(12)(13)(14)(15)(16)(17). Observe the oral cavity squamous cell carcinoma (OCSCC) as an example, the prevalence of PD-L1 positivity has been reported in 45-87% of cases, depending on the cut-off value for positivity, whether cytoplasmic staining was counted as positive, and inclusion of the proportion of HPV+ cancer cases (2,11).…”
Section: Scope Of Problemsmentioning
confidence: 99%
“…Though limited by a small sample size of 10 patients, we confirmed PD-L1 upregulation with evidence of weak cytoplasmic PD-L1 expression in 50% of cases. Though differing from the intense membranous pattern of expression in epithelial malignancies that respond to PD-L1/PD-1 blockade in vivo , PD-L1–positive KS was associated with greater T-cell and macrophage infiltrate, hallmarks of an exhausted immune response to cancer 47 .…”
Section: Recent Advancesmentioning
confidence: 70%