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A global database for modeling tumor-immune cell communication.

ABSTRACT: Communications between tumor cells and surrounding immune cells help shape the tumor immunity continuum. Recent breakthroughs in high-throughput technologies as well as computational algorithms had reported many important tumor-immune cell (TIC) communications, which were scattered in thousands of published studies and impeded systematical characterization of the TIC communications across cancer. Here, a comprehensive database, TICCom, was developed to model TIC communications, containing 739 experimentally-validated or manually-curated interactions collected from more than 3,000 literatures as well as 4,537,709 predicted interactions inferred via six computational algorithms by reanalyzing 32 scRNA-seq datasets and bulk RNA-seq data across 25 cancer types. The communications between tumor cells and 14 types of immune cells were characterized, and the involved ligand-receptor interactions were further integrated. 14190 human and 3650 mouse integrated ligand-receptor interactions with supplemented corresponding function information were also stored in the TICCom database. Our database would serve as a valuable resource for investigating TIC communications.

SUBMITTER: Xie Y

PROVIDER: S-EPMC10338499 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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A global database for modeling tumor-immune cell communication.

Xie Yunjin Y Zhou Weiwei W Shi Jingyi J Xu Mengjia M Lin Zijing Z Li Donghao D Li Jianing J Cheng Shujun S Shao Tingting T Xu Juan J

Scientific data 20230712 1

Communications between tumor cells and surrounding immune cells help shape the tumor immunity continuum. Recent breakthroughs in high-throughput technologies as well as computational algorithms had reported many important tumor-immune cell (TIC) communications, which were scattered in thousands of published studies and impeded systematical characterization of the TIC communications across cancer. Here, a comprehensive database, TICCom, was developed to model TIC communications, containing 739 ex ...[more]

PMID: 37438390

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Project description:Simple Summary CellCall is an R package tool that is used to analyze cell–cell communication based on transcription factor (TF) activities calculated by cell-type specificity of target genes and thus cannot directly handle two-condition comparisons. We developed CellCallEXT to complement CellCall. CellCallEXT can directly identify ligand–receptor (L–R) interactions that alter the expression profiles of downstream genes between two conditions, such as tumor and healthy tissue. Scoring in CellCallEXT quantitatively integrates expression of ligands, receptors, TFs, and target genes (TGs). The pathway enrichment analysis and visualization modules allow biologists to investigate how disease alters cell–cell communication. Furthermore, Reactome pathways were added into CellCallEXT to expand the L–R–TF database. Abstract (1) Background: Single-cell RNA sequencing (scRNA-seq) data are useful for decoding cell–cell communication. CellCall is a tool that is used to infer inter- and intracellular communication pathways by integrating paired ligand–receptor (L–R) and transcription factor (TF) activities from steady-state data and thus cannot directly handle two-condition comparisons. For tumor and healthy status, it can only individually analyze cells from tumor or healthy tissue and examine L–R pairs only identified in either tumor or healthy controls, but not both together. Furthermore, CellCall is highly affected by gene expression specificity in tissues. (2) Methods: CellCallEXT is an extension of CellCall that deconvolutes intercellular communication and related internal regulatory signals based on scRNA-seq. Information on Reactome was retrieved and integrated with prior knowledge of L–R–TF signaling and gene regulation datasets of CellCall. (3) Results: CellCallEXT was successfully applied to examine tumors and immune cell microenvironments and to identify the altered L–R pairs and downstream gene regulatory networks among immune cells. Application of CellCallEXT to scRNA-seq data from patients with deficiency of adenosine deaminase 2 demonstrated its ability to impute dysfunctional intercellular communication and related transcriptional factor activities. (4) Conclusions: CellCallEXT provides a practical tool to examine intercellular communication in disease based on scRNA-seq data.

Project description:The interaction of neoplastic cells with their tumor microenvironment (TME) is required for cancer progression. However, in vitro cancer models, including recent in vitro 3-dimensional (3D) organoid cultures of primary human tumors, are typically comprised exclusively of neoplastic epithelium, with stromal and/or immune interactions requiring artificial reconstitution. As relevant to cancer immunotherapy, the unified co-culture of primary tumor epithelia with their endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has remained particularly elusive. Here, we used a single 3D air-liquid interface (ALI) methodology to successfully propagate 3D Patient-Derived Tumor Organoids (PDOs) as primary tumor epithelia together with native immune and myofibroblast stromal compartments without reconstitution. Derived from >100 diverse human surgically resected tumor samples or from murine tumors in syngeneic immunocompetent mice, PDOs preserved cancer histologic subtypes and mutational spectrum with endogenous T, B, NK cells and macrophages integrally embedded amidst the tumor epithelium. PDO-based TILs accurately recapitulated the T cell receptor (TCR) spectrum of the original tumors, as determined by a robust droplet-based immune profiling solution that links gene expression and immune repertoire in single cells. Anti-PD-1 or anti-PD-L1 treatment of organoids from murine tumors from syngeneic immunocompetent hosts induced activation and cytolytic activity of tumor antigen-specific TILs, indicating successful PDO modeling of immune checkpoint blockade (ICB) and anti-tumor immunity. Crucially, the anti-PD-1 antibody nivolumab activated TILs in PDOs from human lung, renal and melanoma clinical tumor resections. The organoid-based propagation of primary tumor epithelium en bloc with its endogenous immune stroma should facilitate mechanistic investigation of TME-specific local tumor immunity, with applications for functional testing of individualized patient immunotherapy responses.

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A global database for modeling tumor-immune cell communication.

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A global database for modeling tumor-immune cell communication.

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