TumorDecon-Inrtroduction

Tumors consist of many different cell types, including various immune cells, fibroblasts and epithelial cells. Importantly, each tumor has its own unique variation of immune cells resulting in different responses to the same treatments. Documenting these immune variations will help us to understand the process of tumorigenesis and find ways to arrive at effective treatments.

There are many players involved in the tumorigenesis and the inflammatory processes triggered by cancer treatments. Some of the key players are necrotic cells, wild-type and mutant epithelial cells, immune cells, including dendritic cells (DCs), macrophages, and T-cells. For instance, in many solid tumors, necrotic cells release damage-associated molecular pattern molecules (DAMPs) causing activation of DCs, which leads to activation of T-cells. Activated CD4+ T-cells release IL-2, 4, 5, 13 and 17 to activate killer cells like CD8+ T-cells. CD4+ T-cells also release IFN-γ to activate M1 macrophages. Activated macrophages and CD4+ effector T-cells release proliferation signals such as IL-6. As a result, mutant and wild-type epithelial cells receiving proliferation signals compete to divide and take over the available empty spaces generated by treatments. The rate of occurrences of each of these reactions depends on the number of each cell type in the tumor. For this reason, many experimental approaches such as single cell analysis tools, including immunohistochemistry and flow cytometry have been utilized to document tumor immune infiltrates, however these methods are expensive and time consuming. In recent years, several tumor deconvolution methods have been developed to estimate the number of each cell types in a tumor from the gene expression profile of the tumor. These methods require the gene signature of each cell type as their input.