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Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures
- Source :
- Journal for Immunotherapy of Cancer, Journal for ImmunoTherapy of Cancer, Vol 9, Iss 6 (2021)
- Publication Year :
- 2021
-
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.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
sarcoma
medicine.medical_treatment
Immunology
Programmed Cell Death 1 Receptor
Case Report
medicine.disease_cause
Undifferentiated Pleomorphic Sarcoma
03 medical and health sciences
0302 clinical medicine
medicine
Biomarkers, Tumor
Immunology and Allergy
Humans
RC254-282
Pharmacology
Mutation
Tumor microenvironment
business.industry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Cell Differentiation
Immunotherapy
Middle Aged
medicine.disease
Blockade
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Scalp
tumor biomarkers
Cancer research
Molecular Medicine
Sarcoma
business
CD8
Subjects
Details
- ISSN :
- 20511426
- Volume :
- 9
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal for immunotherapy of cancer
- Accession number :
- edsair.doi.dedup.....8ef2c14d93b771f05b79e452ed72cefd