Journal Article

DKFZ-2020-00018

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Immune profiling of human tumors identifies CD73 as a combinatorial target in glioblastoma.

Goswami, S. ; Walle, T. (First author)DKFZ* ; 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.

2020
Nature America Inc. New York, NY

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Please use a persistent id in citations: doi:10.1038/s41591-019-0694-x

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.

Note: 26 (1), 39-46Jan 2020 / #EA:E055#

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Contributing Institute(s):

1. E055 KKE Molekulare Radioonkologie (E055)

Research Program(s):

1. 315 - Imaging and radiooncology (POF3-315) (POF3-315)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 30 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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