Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade
BackgroundCD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response to immunotherapy.MethodsHere, we test this by combining high-dimensional single-c...
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Published in | Journal for immunotherapy of cancer Vol. 9; no. 4; p. e002231 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
BMJ Publishing Group LTD
01.04.2021
BMJ Publishing Group |
Series | Original research |
Subjects | |
Online Access | Get full text |
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Summary: | BackgroundCD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response to immunotherapy.MethodsHere, we test this by combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled in lung and bladder cancer clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)).ResultsITGAE was identified as the most significantly upregulated gene in inflamed tumors. Tumor CD103+ CD8+ TRM cells exhibited a complex phenotype defined by the expression of checkpoint regulators, cytotoxic proteins, and increased clonal expansion.ConclusionsOur analyses indeed demonstrate that the presence of CD103+ CD8+ TRM cells, quantified by tracking intratumoral CD103 expression, can predict treatment outcome, suggesting that patients who respond to PD-1/PD-L1 blockade are those who exhibit an ongoing antitumor T-cell response. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 SM, JG and WEO are joint senior authors. RB and ASC are joint first authors. |
ISSN: | 2051-1426 2051-1426 |
DOI: | 10.1136/jitc-2020-002231 |