Abstract:The tumor immune microenvironment is the micro⁃structure surrounding tumor cells, which plays an indispensable
role in tumorigenesis and tumor progression. It is also the core area targeted by a variety of immunotherapies and is impacted by
complicated factors. Many studies have revealed multiple regulatory mechanisms that promote immune tolerance and immune escape
in the tumor immune microenvironment, including the upregulation of immune checkpoint molecules, the loss of antigen presentation
and the metabolic reprogramming of immune cells. Fatty acid metabolism is an essential metabolic process in the immune
microenvironment and can reprogram under the condition of tumor signaling and nutrient competition. It has been emerging as a hotspot
in recent years. In this review, we focus on the regulatory mechanism of fatty acid metabolism on the survival and functions of immune
cells such as effector T cells, memory T cells, regulatory T cells, and tumor⁃associated macrophages in the tumor immune
microenvironment. We then discuss how fatty acid metabolic reprogramming of immune cells affects the treatment efficacy of
immunotherapies, such as immune checkpoint blockade therapy, adoptive cell therapy, and tumor therapeutic vaccines. We also
summarize the latest developments of fatty acid⁃related targets and drugs. We point out the unique characteristics and difficulties for
research of fatty acid metabolism in tumor⁃related immune cells. Via this review, we hope to provide new insights for tumor
immunotherapies.