@article {Banchereaue002231, author = {Romain Banchereau and Avantika S. Chitre and Alexis Scherl and Thomas D. Wu and Namrata S. Patil and Patricia de Almeida and Edward E. Kadel, III and Shravan Madireddi and Amelia Au-Yeung and Chikara Takahashi and Ying-Jiun Chen and Zora Modrusan and Jacqueline McBride and Rhea Nersesian and Ehab A. El-Gabry and Mark D. Robida and Jeffrey C. Hung and Marcin Kowanetz and Wei Zou and Mark McCleland and Patrick Caplazi and Shadi Toghi Eshgi and Hartmut Koeppen and Priti S. Hegde and Ira Mellman and W. Rodney Mathews and Thomas Powles and Sanjeev Mariathasan and Jane Grogan and William E O{\textquoteright}Gorman}, title = {Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade}, volume = {9}, number = {4}, elocation-id = {e002231}, year = {2021}, doi = {10.1136/jitc-2020-002231}, publisher = {BMJ Specialist Journals}, 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.Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as supplementary information. All data from bulk RNA sequencing (RNAseq) of patients from the IMvigor210 clinical trial are available within the European Genome-Phenome Archive under accession number EGAS00001002556 and have also been previously published. The resulting data from mass cytometry analyses are deposited in Flowrepository.org. Single-cell RNA and TCR sequencing data used in these studies have previously been published and are available within EGA under studies EGAS00001003993 and EGAS00001003994 and datasets EGAD00001005464 and EGAD00001005465. The bladder tumor dataset obtained from Oh et al., 202061 is publicly available in the NCBI GEO database under accession GSE149652. Coordinates for generation of the UMAP were obtained from the authors. There are restrictions to the availability of bulk RNAseq datasets from patients enrolled in OAK and IMvigor211 clinical trials, but a normalized expression matrix for ITGAE and CD8A, the only genes included from these trials in these studies, is provided as a supplementary file.}, URL = {https://jitc.bmj.com/content/9/4/e002231}, eprint = {https://jitc.bmj.com/content/9/4/e002231.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }