Tumors display an organ-like structure and are composed of heterogenous cell types, including different cancer cells, quiescent and activated fibroblasts, endothelial cells, pericytes, adipocytes, immune cells, extracellular vesicles, the extracellular matrix (ECM), and cytokines surrounding these cells. The complex interactions of cancer cells with normal cells and these other elements are known as the tumor stroma or the tumor microenvironment (TME). The biological behavior of a tumor is not completely determined by cancer cells, as many other kinds of normal cells and components of the TME also greatly affect the initiation, progression, and metastasis of cancer. Uncovering the reciprocal interaction between the components of TME and revealing the related mechanisms would not only deliver a better understanding of carcinogenesis, but also provide an emerging novel biomarker library for cancer diagnosis.

This special issue aims to focus on recent advances of TME-related studies and their contribution to early diagnosis of cancers. Studies concerning the function of TME components and their application in diagnosis are anticipated. Studies employing multiplexed in situ imaging or other advanced imaging techniques for the characterization of the TME are particularly welcomed. The special issue welcomes both original research articles and focused reviews.

Potential topics include but are not limited to the following:

• Roles of different cellular and structural components of the TME and related mechanisms
• Biomarker discovery and mechanism studies based on TME components, especially ECMs
• Interaction between stroma components and cancer cells
• Microvesicles and exosomes in the TME and their application in diagnosis