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Deep single-cell RNA sequencing data for 11138 T cells from tumour, adjacent normal tissue and peripheral blood of treatment-naive CRC patients. The DATA ACCESS AGREEMENT is provided at https://github.com/zhangyybio/single-T-cell-data-access. Applicants can request access to the data by directly downloading it or by sending an email to cancerpku@pku.edu.cn. The process that is used to approve an application includes verifying the institution, participants and research purposes of the application. In general this process will take about two weeks. In principal, any scientific research program complying with the laws and bioethic regulation policies of China will be approved.

ABSTRACT: T cells are central players in cancer immunotherapy1, yet some of their fundamental properties such as development and migration within tumours remain elusive. The enormous T cell receptor (TCR) repertoire, required for recognising foreign and self-antigens2,3, could serve as lineage tags to track these T cells in tumours4. Here, we obtained transcriptomes of 11,138 single T cells from 12 colorectal cancer (CRC) patients and developed STARTRAC (Single T-cell Analysis by Rna-seq and Tcr TRACking) indices to quantitatively analyse dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. While both CD8+ effector and “exhausted” T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, the majority of tumour-infiltrating Tregs showed clonal exclusivity, whereas certain Treg clones were developmentally linked to multiple TH clones. Notably, we identified two IFNG+ TH1-like clusters in tumours, the GZMK+ TEM and CXCL13+ TH1-like clusters, which were associated with distinct IFN-γ-regulating transcription factors, EOMES/RUNX3 and BHLHE40, respectively. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in tumours of microsatellite-instable (MSI) patients, which might explain their favourable response rates to immune-checkpoint blockade. Furthermore, we found IGFLR1 to be highly expressed in both CXCL13+BHLHE40+ TH1-like and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provides a powerful avenue to comprehensively dissect the T cell properties in CRC, which could shed new insights into the dynamic relationships of T cells in other cancers

PROVIDER: EGAS00001002791 | EGA |

REPOSITORIES: EGA

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Project description:The paper describes a model of interaction of Th cells and macrophage in melanoma. Created by COPASI 4.25 (Build 207) This model is described in the article: Modelling and investigation of the CD4 T cells – Macrophages paradox in melanoma immunotherapies Raluca Eftimie, Haneen Hamam Journal of Theoretical Biology 420 (2017) 82–104 Abstract: It is generally accepted that tumour cells can be eliminated by M1 anti-tumour macrophages and CD8+ T cells. However, experimental results over the past 10–15 years have shown that B16 mouse melanoma cells can be eliminated by the CD4+ T cells alone (either Th1 or Th2 sub-types), in the absence of CD8+ T cells. In some studies, elimination of B16 melanoma was associated with a Th1 immune response (i.e., elimination occurred in the presence of cytokines produced by Th1 cells), while in other studies melanoma elimination was associated with a Th2 immune response (i.e., elimination occurred in the presence of cytokines produced by Th2 cells). Moreover, macrophages have been shown to be present inside the tumours, during both Th1 and Th2 immune responses. To investigate the possible biological mechanisms behind these apparently contradictory results, we develop a class of mathematical models for the dynamics of Th1 and Th2 cells, and M1 and M2 macrophages in the presence/absence of tumour cells. Using this mathematical model, we show that depending on the re- polarisation rates between M1 and M2 macrophages, we obtain tumour elimination in the presence of a type-I immune response (i.e., more Th1 and M1 cells, compared to the Th2 and M2 cells), or in the presence of a type- II immune response (i.e., more Th2 and M2 cells). Moreover, tumour elimination is also possible in the presence of a mixed type-I/type-II immune response. Tumour growth always occurs in the presence of a type-II immune response, as observed experimentally. Finally, tumour dormancy is the result of a delicate balance between the pro-tumour effects of M2 cells and the anti-tumour effects of M1 and Th1 cells. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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