Turning Cold into Hot: New Insights in Cancer Immunotherapy

The tumor microenvironment (TME) is essential for cancer maintenance and is responsible for several antitumor characteristics, such as immune system avoidance, resistance to anticancer therapies, invasion, and metastasis. The TME is composed of several components, including fibroblasts, extracellular matrix proteins, pericytes, and immune cells. The immune cells, including T-lymphocytes, are responsible for fighting cancer cells, inducing cell death. However, cancer cells develop several mechanisms to avoid the immune system, including mutations to change the antigens originally recognized by T cells. Tumors that can avoid the immune system, including the T-cell antitumor response, are known as nonimmunogenic tumors or “cold” tumors. The main characteristic of this tumor subtype is lack of response to immunotherapy drugs. In contrast, immunogenic, or “hot” tumors have an active T-cell antitumor response and respond well to immunotherapy. Therefore, turning cold tumors into hot tumors by stimulation of T-cell infiltration is a key strategy for the development of successful immunotherapies. This chapter will introduce the concept of cold and hot tumors and discuss the potential strategies to stimulate T-cell infiltration in cold tumors.