Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade.

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.

• Authors: 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, Zora Modrusan, Jacqueline McBride, Rhea Nersesian, Ehab A El-Gabry, Mark D Robida, Jeffrey C Hung, Marcin Kowanetz, Wei Zou, Mark McCleland, Patrick Caplazi, Shadi Toghi Eshgi, Hartmut Koeppen, Priti S Hegde, Ira Mellman, W Rodney Mathews, Thomas Powles, Sanjeev Mariathasan, Jane Grogan, William E O'Gorman
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 9 Issue 4 (04 2021) ISSN: 2051-1426 [Electronic] England
• PMID: 33827905 (Publication Type: Journal Article)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antigens, CD
• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• Immune Checkpoint Inhibitors
• Integrin alpha Chains
• alpha E integrins
• atezolizumab

Topics

• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Antigens, CD (genetics)
• B7-H1 Antigen (antagonists & inhibitors, immunology)
• Biomarkers, Tumor (genetics)
• CD8-Positive T-Lymphocytes (immunology)
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Databases, Genetic
• Gene Expression Profiling
• Humans
• Immune Checkpoint Inhibitors (adverse effects, therapeutic use)
• Integrin alpha Chains (genetics)
• Lung Neoplasms (drug therapy, genetics, immunology)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Phenotype
• Randomized Controlled Trials as Topic
• Time Factors
• Treatment Outcome
• Tumor Microenvironment
• Urinary Bladder Neoplasms (drug therapy, genetics, immunology)