Single cell transcriptome analysis of human tumor-infiltrating T regulatory cells
M. De Simone1, G. Rossetti1, P. Gruarin1, V. Ranzani1, S. Mazzara1, RJP Bonnal1,
S. Abrignani1,2, M. Pagani1,3*
1Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi', Milan 20122, Italy;
2Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano 20122, Italy; 3Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milano 20129, Italy
* Corresponding author
Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. We provided a comprehensive RNA-sequencing analysis of CD4+ effector cells (Th1 and Th17) and regulatory T cells (Treg) infiltrating colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). These data were integrated by transcriptomic data obtained from the same subsets isolated from adjacent healthy tissues to obtain the expression landscape of transcription factors, membrane receptors, cytokines and immune checkpoints of tumor infiltrating lymphocytes in NSLC and CRC samples. We showed that tumor infiltrating Treg cells are described by the expression of a subset of specific signature genes. We found tumor-infiltrating Treg cells are highly suppressive, upregulate several immune-checkpoints, and express on the cell surface specific signature molecules such as IL1R2, PD-1 Ligand1, PD-1 Ligand2, and CCR8, which were not previously described on Treg cells. Moreover, we performed single cell transcriptomic analysis of more than two thousands tissue infiltrating Treg cells. Analysis of these data suggests an heterogeneity of these cells that cannot be appreciated at the population level. These findings illustrates the importance of studying Treg cells contextually at tumor sites to better elucidate the underlying mechanisms of localized immune responses and define new potential targets for immune-based cancer therapy.
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