The human body exhibits a diverse range of cells that undergo transit from one state to another in life (development, disease, and regeneration). Though derived from the same zygote, the cell, with its types and states, is greatly influenced by the internal processes and external factors (Song et al.,2019). In its progression through proliferation and the differentiation states to generate multiple cell types for organ formation, complex heterogeneities in the cellular architecture are observed. The cellular heterogeneity in terms of morphology, function, and gene expression profiles lie between various tissues, but has also been observed among the same cell types that allow them to perform different roles. Dysregulation in any particular cell type (irrespective of tissues, organs, and organ system) influences the entire system that progresses to disorders and even severe diseases like cancer. Recent technological advancements have enabled biologists to profile cells at individual levels on a variety of omics layers (genomes, transcriptomes, epigenomes, and proteomes) (Hu et al., 2016); among these, single cell (SC) transcriptomics is widely studied. The cells of a human body, being heterogeneous, often show a drastic variation at the individual level (Wang and Bodovitz, 2010; Xin et al., 2016), and the study of single cell transcriptomics has enabled us to understand the fate of cells, their transition to different subtypes, and the dynamics of gene expression masked in bulk population studies (Altschuler and Wu, 2010; Trapnell et al., 2014).
BREAST CANCER
Breast cancer is a disease in which cells in the breast grow out of control. There are several different kinds of breast cancer. The form of breast cancer depends on which cell types in the breast turn into cancer. It can be treated several ways. Choosing a treatment depends on the kind of breast cancer and how far it has spread. An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses proteins (or "checkpoints") on immune cells that need to be turned on (or off) to start an immune response. Breast cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Drugs that target these checkpoint proteins help restore the immune response against breast cancer cells.
Recently, the development of immunotherapy through the immune checkpoint blockade led to long-lasting responses in several types of cancers that are resistant to conventional treatments, like melanoma and non-small cell lung cancer. Immunotherapy has also demonstrated significant improvements in various other types of cancers. However, breast cancer remains one of the types that has not experienced the explosion of immunotherapy treatment yet. Indeed, breast cancer was traditionally considered as being weakly immunogenic with a lower mutational load compared to other tumor types. Pembrolizumab (Keytruda) is a drug that targets PD-1 (programmed death-ligand 1) , a protein on immune system T cells that normally helps keep them from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against breast cancer cells. This can often shrink tumors and can be used with chemotherapy to treat triple-negative breast cancer.
These drugs remove one of the protections on the body's immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs. In the last few years, anti-PD 1/PD-L1 agents have been evaluated in breast cancer, particularly in the triple negative subtype, with promising results observed when delivered as monotherapy or in combination with conventional treatments. In this example project, we will look at a single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer. To learn more about the study, you can visit: https://pubmed.ncbi.nlm.nih.gov/33958794/
You can run the demo pipeline on the T-Bioinfo Server to learn the flow of steps in the pipeline and visualize the results obtained: https://server.t-bio.info/pipelinessinglecellrnaanalysisinseurat/demopipelines/demo-breast-cancer-seurat-10x
To get more insights about the project, run the pipelines and learn to interpret results, you can visit the example project on the OmicsLogic Learn Portal:
https://learn.omicslogic.com/courses/course/project-15-tumor-heterogeneity-of-breast-cancer