Immune profiling of human tumors identifies CD73 as a combinatorial target in glioblastoma Research Letter


Authors: Goswami, S.; Walle, T.; Cornish, A. E.; Basu, S.; Anandhan, S.; Fernandez, I.; Vence, L.; Blando, J.; Zhao, H.; Yadav, S. S.; Ott, M.; Kong, L. Y.; Heimberger, A. B.; de Groot, J.; Sepesi, B.; Overman, M.; Kopetz, S.; Allison, J. P.; Pe’er, D.; Sharma, P.
Title: Immune profiling of human tumors identifies CD73 as a combinatorial target in glioblastoma
Abstract: Immune checkpoint therapy with anti-CTLA-4 and anti-PD-1/PD-L1 has revolutionized the treatment of many solid tumors. However, the clinical efficacy of immune checkpoint therapy is limited to a subset of patients with specific tumor types1,2. Multiple clinical trials with combinatorial immune checkpoint strategies are ongoing; however, the mechanistic rationale for tumor-specific targeting of immune checkpoints is elusive. To garner an insight into tumor-specific immunomodulatory targets, we analyzed 94 patients representing five different cancer types, including those that respond relatively well to immune checkpoint therapy and those that do not, such as glioblastoma multiforme, prostate cancer and colorectal cancer. Through mass cytometry and single-cell RNA sequencing, we identified a unique population of CD73hi macrophages in glioblastoma multiforme that persists after anti-PD-1 treatment. To test if targeting CD73 would be important for a successful combination strategy in glioblastoma multiforme, we performed reverse translational studies using CD73−/− mice. We found that the absence of CD73 improved survival in a murine model of glioblastoma multiforme treated with anti-CTLA-4 and anti-PD-1. Our data identified CD73 as a specific immunotherapeutic target to improve antitumor immune responses to immune checkpoint therapy in glioblastoma multiforme and demonstrate that comprehensive human and reverse translational studies can be used for rational design of combinatorial immune checkpoint strategies. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords: controlled study; major clinical study; nonhuman; letter; colorectal cancer; animal cell; mouse; gene targeting; animal experiment; animal model; prostate cancer; glioblastoma; macrophage; rna sequence; 5' nucleotidase; human; priority journal; mass cytometry
Journal Title: Nature Medicine
Volume: 26
Issue: 1
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2020-01-01
Start Page: 39
End Page: 46
Language: English
DOI: 10.1038/s41591-019-0694-x
PUBMED: 31873309
PROVIDER: scopus
PMCID: PMC7182038
DOI/URL:
Notes: Source: Scopus
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  1. Dana Pe'er
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