The tissue microenvironment changes into a tumor environment (TME) when cancer cells proliferate by secreting signals that attract other cell types. The tumor cells modify the ECM and, together by the interactions with other cell types, create a supportive environment for their own growth and invasion.
The fibroblasts and endothelial cells recruited at the cancer site release cytokines, growth factors, and ECM proteins, which stimulate angiogenesis and oncogenesis enabling the cancer cells to proliferate and invade nearby tissues.
By producing specific signals to boost their own growth and survival, tumor cells trick the immune system by manipulating the T cells, B cells, and macrophages that typically defend and repair damaged tissue.
Given the variety of cells and molecules that comprise the TME, dissecting its complexity is critical since it can provide clues as to why some cancers respond well to a particular treatment while others do not respond at all or acquire resistance over time. This amount of data can aid in the identification of prospective biomarkers for tailored immunotherapies, resulting in a more predictable clinical outcome

Changes in the components of the tissue microenvironment (the ECM and glial cells) result in neurodegeneration. This progressive loss of structure or function of the neurons can lead to diseases such as Alzheimer’s, Parkinson’s, and Huntington’s.
For example, in Alzheimer’s disease the ECM becomes more rigid, which impairs the ability of neurons to communicate with each other. Misfolded protein aggregates accumulate both within neuronal cells and extracellularly. In Parkinson’s disease, there is an accumulation of abnormal proteins in the ECM. Glial cells, including astrocytes and microglia, release pro-inflammatory cytokines, causing neuroinflammation and neuronal damage.
To help identify new targets for therapy, it is critical to understand how the tissue microenvironment contributes to neurodegeneration.

The tissue microenvironment can influence the function, activation, regulation, and survival of immune cells. This is essential to keep in mind while addressing autoimmune diseases.
In multiple sclerosis, for example, the central nervous system (CNS) tissue microenvironment activates immune cells to target myelin, the protective layer around nerve cells, resulting in neuronal damage. The tissue microenvironment in the synovium becomes inflamed in rheumatoid arthritis and releases cytokines, chemokines, and other molecules that attract immune cells to the site of inflammation. The T cells and B cells interact with the tissue microenvironment causing production of autoantibodies resulting in a sustained inflammatory response.
Designing tailored therapies that can modulate the immune response and avoid tissue damage requires an understanding of the role of the tissue microenvironment in autoimmune disorders.

The tissue microenvironment plays a critical role in infectious diseases by influencing pathogen virulence, immune responses, and the efficacy of antimicrobial therapies.
For example, certain immune cells such as macrophages and dendritic cells help in recognizing and responding to invading pathogens, while a large population of regulatory T cells in specific organs may inhibit the immune response.
The tissue microenvironment impacts the efficacy of antimicrobial therapy. Certain tissues have barriers that prevent drug penetration, whereas some pathogens resist antimicrobial treatments by adapting to the tissue microenvironment.
Understanding this interplay between pathogens and the tissue microenvironment is thus essential for the development of new therapeutic strategies.

After establishing the significance of investigating the tissue microenvironment, it is now essential to understand the need of the hour. Precision medicine is a new area that aims to develop personalized treatment plans that are tailored to each patient's unique traits. Precision medicine can comprehend the context in which a disease arises in a patient and help design personalized therapies by interrogating the patient's tissue microenvironment.