The study of cancer biology should be based around a comprehensive vision of the
entire tumor ecosystem, considering the functional, bioenergetic and metabolic state of tumor cells
and those of their microenvironment, and placing particular importance on immune system cells.
Enhanced understanding of the molecular bases that give rise to alterations of pathways related
to tumor development can open up new therapeutic intervention opportunities, such as metabolic
regulation applied to immunotherapy. This review outlines the role of various oncometabolites
and immunometabolites, such as TCA intermediates, in shaping pro/anti-inflammatory activity
of immune cells such as MDSCs, T lymphocytes, TAMs and DCs in cancer. We also discuss the
extraordinary plasticity of the immune response and its implication in immunotherapy efficacy, and
highlight different therapeutic intervention possibilities based on controlling the balanced systems of
specific metabolites with antagonistic functions
