Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade. Issue 4 (7th April 2021)

• Record Type: Journal Article
• Authors: Banchereau, Romain; Chitre, Avantika S.; Scherl, Alexis; Wu, Thomas D.; Patil, Namrata S.; de Almeida, Patricia; Kadel, III, Edward E.; Madireddi, Shravan; Au-Yeung, Amelia; Takahashi, Chikara; Chen, Ying-Jiun; Modrusan, Zora; McBride, Jacqueline; Nersesian, Rhea; El-Gabry, Ehab A.; Robida, Mark D.; Hung, Jeffrey C.; Kowanetz, Marcin; Zou, Wei; McCleland, Mark; Caplazi, Patrick; Eshgi, Shadi Toghi; Koeppen, Hartmut; Hegde, Priti S.; Mellman, Ira; Mathews, W. Rodney; Powles, Thomas; Mariathasan, Sanjeev; Grogan, Jane; O'Gorman, William E
• Is Part Of: Journal for immunotherapy of cancer. Volume 9:Issue 4(2021)
• Publication Date: 2021-04-07
• Subjects: biomarkers -- tumor -- CD8-positive T-lymphocytes -- gene expression profiling -- immunotherapy -- lymphocytes -- tumor-infiltrating; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-002231
• Languages: English
• ISSNs: 2051-1426

Abstract

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.