Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures

Laurene S. Cheung, Lingling Chen, Teniola F. Oke, Thomas B. Schaffer, Karim Boudadi, Jillian T. Ngo, John Mc Mahon Gross, Holly Kemberling, Luis A. DIaz, Evan Lipson, John William Sidhom, Janis Taube, Robert Anders, Drew M. Pardoll, Dung T. Le, Christian F. Meyer, Nicolas Llosa

Research output: Contribution to journalArticlepeer-review

Abstract

Undifferentiated pleomorphic sarcoma (UPS), an aggressive soft-tissue sarcoma of adults, has been characterized by low tumor mutational burden (TMB) and high copy number alterations. Clinical trials of programmed death-1 (PD-1) blockade in UPS have reported widely varying efficacy. We describe two patients with recurrent scalp UPS that experienced clinical benefit from PD-1 blockade. These tumors had high TMB with a UV-induced mutational pattern. Analysis of additional head and neck UPS cases identified five out of seven tumors with high TMB and an ultraviolet (UV) mutational signature. Head and neck UPS tumors also had increased programmed death-ligand 1 (PD-L1) expression and CD8+ T cell infiltration as compared with UPS tumors arising from other sites. In summary, we found that UPS tumors of the head and neck, but not elsewhere, have a PD-L1+, T-cell-inflamed tumor microenvironment and high TMB, suggesting that these tumors represent a distinct genetic subgroup of UPS for which immune checkpoint inhibitor therapy might be effective.

Original languageEnglish (US)
Article number002345
JournalJournal for immunotherapy of cancer
Volume9
Issue number6
DOIs
StatePublished - Jun 8 2021

Keywords

  • Immunotherapy
  • sarcoma
  • tumor biomarkers

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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