Macrophages orchestrate immune responses that can either hamper (left) or foster
(right) the effectiveness of conventional anticancer strategies.
On the left: cytotoxic agents enhance tumor infiltration by immunosuppressive
macrophages, which activate chemoprotective T cells and tame adaptive immune
responses; chemotherapy or radiotherapy-induced tissue damage triggers the
recruitment of immunosuppressive myeloid cells, which orchestrate a misdirected
tissue-repair response, promoting tumor growth and revascularization;
macrophages, an essential component of tissue stem cell niches, can protect CSC
against cytotoxicity.
On the right: selected chemotherapeutic agents (e.g Doxorubicin) increase the
immunogenicity of malignant cells (immunogenic cell death), which stimulate
myeloid cells to differentiate into antigen presenting cells and trigger
effective adaptive immune responses; anticancer agents like Gemcitabine can
directly skew macrophage effector functions towards an antitumor mode and
increase their cytotoxicity, resulting into a favorable synergism; neoadjuvants
low-dose γ-irradiation set macrophage functions in an antitumor mode,
promoting regression at sites distant from irradiated lesions (abscopal effect).
CSC: cancer stem cells.