Expression of PD-1 and PD-Ls in Kaposi's sarcoma and regulation by oncogenic herpesvirus lytic reactivation

Virology. 2019 Oct:536:16-19. doi: 10.1016/j.virol.2019.07.024. Epub 2019 Jul 30.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) causes several cancers such as Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). PD-1/PD-Ls immune checkpoint molecules play important roles in cancer cell immune escape. The expression of PD-1/PD-Ls and their regulation by oncogenic viruses, in particular KSHV, remain largely undefined. Here we demonstrate strong PD-1/PD-L1/PD-L2 expression in KS tissues from a cohort of HIV + patients. We found that induction of KSHV lytic reactivation significantly upregulates PD-L1 expression on infected tumor cells, potentially through several major cellular signaling pathways and IL-1β, which may represent a novel mechanism for virus-associated tumor cell immune escape.

Keywords: KSHV; Kaposi's sarcoma; PD-1; PD-L1; PD-L2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / immunology
  • Cell Line, Tumor
  • Cohort Studies
  • Coinfection
  • Gene Expression Regulation
  • HEK293 Cells
  • HIV / immunology
  • HIV / pathogenicity
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / virology
  • Herpesvirus 8, Human / genetics*
  • Herpesvirus 8, Human / immunology
  • Herpesvirus 8, Human / pathogenicity
  • Host-Pathogen Interactions / genetics*
  • Host-Pathogen Interactions / immunology
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Ligand 2 Protein / genetics*
  • Programmed Cell Death 1 Ligand 2 Protein / immunology
  • Programmed Cell Death 1 Receptor / genetics*
  • Programmed Cell Death 1 Receptor / immunology
  • Sarcoma, Kaposi / genetics*
  • Sarcoma, Kaposi / immunology
  • Sarcoma, Kaposi / virology
  • Signal Transduction
  • Tumor Escape / genetics
  • Virus Activation
  • Virus Latency

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • IL1B protein, human
  • Interleukin-1beta
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor