Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures
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 p...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2021-06-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/6/e002345.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850192747305107456 |
|---|---|
| author | Drew M Pardoll Evan Lipson John-William Sidhom Karim Boudadi Robert Anders Dung T Le Luis A Diaz Nicolas Llosa Janis Taube Lingling Chen Teniola F Oke Christian F Meyer Laurene S Cheung Thomas B Schaffer Jillian T Ngo John McMahon Gross Holly Kemberling |
| author_facet | Drew M Pardoll Evan Lipson John-William Sidhom Karim Boudadi Robert Anders Dung T Le Luis A Diaz Nicolas Llosa Janis Taube Lingling Chen Teniola F Oke Christian F Meyer Laurene S Cheung Thomas B Schaffer Jillian T Ngo John McMahon Gross Holly Kemberling |
| author_sort | Drew M Pardoll |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-49dd5e69ccc04ef2b5cc0e561cbddcbd |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-49dd5e69ccc04ef2b5cc0e561cbddcbd2025-08-20T02:14:27ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-06-019610.1136/jitc-2021-002345Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signaturesDrew M Pardoll0Evan Lipson1John-William Sidhom2Karim Boudadi3Robert Anders4Dung T Le5Luis A Diaz6Nicolas Llosa7Janis Taube8Lingling Chen9Teniola F Oke10Christian F Meyer11Laurene S Cheung12Thomas B Schaffer13Jillian T Ngo14John McMahon Gross15Holly Kemberling162 Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA2 Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA1 Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland, USA2 Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA7Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA2 Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA5 Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA6Johns Hopkins Medicine, Baltimore, MD, USA4 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA1 Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland, USA1 Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland, USA2 Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA1 Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland, USA3 NextCure Inc, Beltsville, Maryland, USA1 Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland, USA4 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA2 Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USAUndifferentiated 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.https://jitc.bmj.com/content/9/6/e002345.full |
| spellingShingle | Drew M Pardoll Evan Lipson John-William Sidhom Karim Boudadi Robert Anders Dung T Le Luis A Diaz Nicolas Llosa Janis Taube Lingling Chen Teniola F Oke Christian F Meyer Laurene S Cheung Thomas B Schaffer Jillian T Ngo John McMahon Gross Holly Kemberling Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures Journal for ImmunoTherapy of Cancer |
| title | Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures |
| title_full | Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures |
| title_fullStr | Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures |
| title_full_unstemmed | Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures |
| title_short | Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures |
| title_sort | anti pd 1 elicits regression of undifferentiated pleomorphic sarcomas with uv mutation signatures |
| url | https://jitc.bmj.com/content/9/6/e002345.full |
| work_keys_str_mv | AT drewmpardoll antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT evanlipson antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT johnwilliamsidhom antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT karimboudadi antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT robertanders antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT dungtle antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT luisadiaz antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT nicolasllosa antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT janistaube antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT linglingchen antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT teniolafoke antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT christianfmeyer antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT laurenescheung antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT thomasbschaffer antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT jilliantngo antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT johnmcmahongross antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures AT hollykemberling antipd1elicitsregressionofundifferentiatedpleomorphicsarcomaswithuvmutationsignatures |