Genomic and immunologic correlates of LAG-3 expression in cancer

Anshuman Panda, Jeffrey A. Rosenfeld, Eric A. Singer, Gyan Bhanot, Shridar Ganesan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Immune checkpoint blockade leads to unprecedented responses in many cancers. Although currently available agents mostly target the PD-1 and CTLA-4 pathways, agents targeting the immune checkpoint protein LAG-3 are under active clinical development, and early clinical data show that LAG-3 expression is a biomarker of response to LAG-3 blockade. To determine which cancers may benefit most from LAG-3 blockade, we performed a pan-cancer analysis of The Cancer Genome Atlas dataset to identify genomic and immunologic correlates of LAG-3 expression. High mutation burden, and expression of exogenous virus (EBV, HPV) or endogenous retrovirus (ERV3-2), were associated with overexpression of LAG-3 in multiple cancers. Although CD8+ T-cell marker (CD8A) and LAG-3 were strongly co-expressed with each other and with PD-L1 in most cancers, there were three notable exceptions: HPV+ head-neck squamous cell cancer, renal cell cancer, and glioblastoma. These results may have important implications for guiding development clinical trials of LAG-3 blockade.

Original languageEnglish (US)
Article number1756116
JournalOncoImmunology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology

Keywords

  • Immune checkpoint blockade
  • LAG-3
  • endogenous retrovirus
  • mutation burden
  • virus

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