Journal for ImmunoTherapy of Cancer (Apr 2021)
Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade
- Marcin Kowanetz,
- Thomas Powles,
- Hartmut Koeppen,
- Jane Grogan,
- Patrick Caplazi,
- Ira Mellman,
- Wei Zou,
- Sanjeev Mariathasan,
- Priti S. Hegde,
- Mark McCleland,
- Jacqueline McBride,
- Zora Modrusan,
- Romain Banchereau,
- Avantika S. Chitre,
- Alexis Scherl,
- Thomas D. Wu,
- Namrata S. Patil,
- Patricia de Almeida,
- Edward E. Kadel, III,
- Shravan Madireddi,
- Amelia Au-Yeung,
- Chikara Takahashi,
- Ying-Jiun Chen,
- Rhea Nersesian,
- Ehab A. El-Gabry,
- Mark D. Robida,
- Jeffrey C. Hung,
- Shadi Toghi Eshgi,
- W. Rodney Mathews,
- William E O'Gorman
Affiliations
- Marcin Kowanetz
- Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Thomas Powles
- Barts Cancer Center, Queen Mary University, London, UK
- Hartmut Koeppen
- Department of Research Pathology, Genentech Inc, South San Francisco, California, USA
- Jane Grogan
- Department of Cancer Immunology, Genentech Inc, South San Francisco, California, USA
- Patrick Caplazi
- Department of Research Pathology, Genentech Inc, South San Francisco, California, USA
- Ira Mellman
- Department of Cancer Immunology, Genentech Inc, South San Francisco, California, USA
- Wei Zou
- Department of Biostatistics Oncology, Genentech Inc, South San Francisco, California, USA
- Sanjeev Mariathasan
- Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Priti S. Hegde
- Foundation Medicine, Cambridge, Massachusetts, USA
- Mark McCleland
- Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Jacqueline McBride
- Department of OMNI Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Zora Modrusan
- Department of Microchemistry, Proteomics, Lipidomics, and Next Generation Sequencing, Genentech Inc, South San Francisco, California, USA
- Romain Banchereau
- Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Avantika S. Chitre
- Department of Cancer Immunology, Genentech Inc, South San Francisco, California, USA
- Alexis Scherl
- Department of Research Pathology, Genentech Inc, South San Francisco, California, USA
- Thomas D. Wu
- Department of Bioinformatics and Computational Biology, Genentech Inc, South San Francisco, California, USA
- Namrata S. Patil
- Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Patricia de Almeida
- Department of Cancer Immunology, Genentech Inc, South San Francisco, California, USA
- Edward E. Kadel, III
- Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Shravan Madireddi
- Department of Cancer Immunology, Genentech Inc, South San Francisco, California, USA
- Amelia Au-Yeung
- Department of OMNI Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Chikara Takahashi
- Department of OMNI Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Ying-Jiun Chen
- Department of Microchemistry, Proteomics, Lipidomics, and Next Generation Sequencing, Genentech Inc, South San Francisco, California, USA
- Rhea Nersesian
- Department of Oncology Biomarker Development, Genentech Inc, South San Francisco, California, USA
- Ehab A. El-Gabry
- Ventana Medical Systems Inc, Tucson, Arizona, USA
- Mark D. Robida
- Ventana Medical Systems Inc, Tucson, Arizona, USA
- Jeffrey C. Hung
- Department of Research Pathology, Genentech Inc, South San Francisco, California, USA
- Shadi Toghi Eshgi
- Department of OMNI Biomarker Development, Genentech Inc, South San Francisco, California, USA
- W. Rodney Mathews
- Department of OMNI Biomarker Development, Genentech Inc, South San Francisco, California, USA
- William E O'Gorman
- Department of OMNI Biomarker Development, Genentech Inc, South San Francisco, California, USA
- DOI
- https://doi.org/10.1136/jitc-2020-002231
- Journal volume & issue
-
Vol. 9,
no. 4
Abstract
Background CD8+ 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.Methods Here, 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)).Results ITGAE 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.Conclusions Our 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.
