The rise of immunotherapy gives new prospects for a cure for cancer. However, in some nonimmunogenic tumors, immunotherapy has failed to demonstrate significant clinical activity, in part due to a complex tumor microenvironment (TME) that provides a formidable barrier to immune infiltration and function.

The TME, comprised of multiple cellular and molecular factors, significantly influences tumor progression and therapeutic response. The complex interactions among tumors, immune cells, and their microenvironment remain to be elucidated. Immune cells can play either a pro- or anti-tumor role and may vary in their activation status within the tumor microenvironment. Both innate immune cells and adaptive immune cells are present and interact with the tumor cells via direct contact or through chemokine and cytokine signaling, which shapes the behavior of the tumor and its response to therapy. In addition, components of the TME also have a broad impact on the immune cells. Up to now, numerous evidence has been provided to suggest that the TME can alter the capacity of the immune system in tumors.

The aim of this Special Issue is to collate original research and review articles that will aid in uncovering the complex interactions between tumors, immune cells, and their microenvironment.

Potential topics include but are not limited to the following:

• The spatial and temporal distribution of immune cells in TME
• Cancer cell-immune cell interaction in TME
• Endothelial cell-immune cell interaction in TME
• Fibroblast-immune cell interaction in TME
• Immune cell-extracellular matrix interaction in TME
• Immune cells in the premetastatic niche
• Crosstalk between the nervous system and TME
• Crosstalk between the endocrine system and TME
• Crosstalk among immune cells
• Clinical perspectives of TME and immune niches