Cancer cell types

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Understanding Cancer Cell Types: Insights from Recent Research

Tumor-Infiltrating Immune Cells in Cancer

Immune Cell Types in Tumors

Immune cells within tumors significantly influence tumor progression and response to therapy. A novel algorithm has been developed to estimate the fraction of cancer and immune cell types from bulk tumor gene expression data, integrating gene expression profiles from major non-malignant cell types found in tumors. This method has been validated using flow cytometry, immunohistochemistry, and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens, enhancing the accuracy and scope of cell fraction predictions from tumor gene expression data.

T Cells in the Tumor Microenvironment

Single-cell RNA sequencing of T cells across 21 cancer types from over 300 patients has revealed significant heterogeneity in T cell states within the tumor microenvironment (TME). This study identified various potentially tumor-reactive T cell populations, including exhausted CD8+ T cells and dual-functional CD4+ T cells, which vary dramatically across different cancer types. These findings highlight the importance of T cell states in influencing clinical outcomes and responses to immunotherapies.

Dendritic Cells and Cancer Immunity

Conventional type 1 dendritic cells (cDC1s) play a crucial role in cancer immunity. These cells are essential for initiating T cell responses, attracting T cells, secreting cytokines, and presenting tumor antigens within the TME. Increasing the abundance and functionality of cDC1s in tumors is a promising strategy to enhance anti-tumor immunity and improve the efficacy of T cell-based immunotherapies.

Cancer Stem Cells (CSCs)

CSCs in Tumor Progression and Therapy

Cancer stem cells (CSCs) are self-renewable cells identified in most liquid and solid cancers. They contribute to tumor onset, expansion, resistance, recurrence, and metastasis. CSCs are characterized by specific cell surface markers, which vary depending on the tumor type. The transition between CSCs and non-CSCs is influenced by signals from the CSC niche and the TME. Effective therapeutic strategies must target both CSCs and non-CSCs to prevent tumor relapse, utilizing approaches such as immunotherapy, hormone therapy, and gene knockout.

The Nature of Cancer Stem Cells

The concept of "stemness" in cancer is debated as either a cell type or a cell state. Stemness may result from the arrest of a linear differentiation process, with key genes like Oct4, Sox2, and Nanog playing crucial roles. This understanding is essential for developing therapies targeting CSCs, as these cells are often more resistant to treatments due to their ability to self-renew and differentiate.

Molecular Classification and Cell-of-Origin Patterns

Integrative Molecular Analyses

Comprehensive molecular analyses of approximately 10,000 tumors from 33 cancer types have shown that cell-of-origin patterns dominate the molecular classification of cancers. Clustering based on DNA methylation, mRNA, and miRNA expression levels revealed that histology, tissue type, or anatomic origin primarily organize these patterns. This integrative approach emphasizes the importance of cell-of-origin in understanding cancer biology and developing targeted therapies.

Epigenomic Deconvolution

Epigenomic deconvolution methods, such as EDec, have been developed to infer cell type composition and molecular profiles within tumors. Applying EDec to breast tumors from The Cancer Genome Atlas (TCGA) revealed changes in immune cell infiltration and stromal composition related to patient prognosis. These findings underscore the role of stromal cells in the metabolic coupling between different cell types within tumors.

Conclusion

Recent research has provided significant insights into the diverse cell types within tumors, including immune cells, cancer stem cells, and the influence of cell-of-origin patterns. Understanding the heterogeneity and dynamics of these cell types is crucial for developing effective cancer therapies and improving patient outcomes. By integrating various molecular and computational approaches, researchers continue to unravel the complexities of the tumor microenvironment and its impact on cancer progression and treatment.