Immune cells in the
tumor micro-environment (TME) establish a complex relationship with
cancer cells and may strongly influence
disease progression and response to
therapy. It is well established that myeloid cells infiltrating
tumor tissues favor
cancer progression. Tumor-Associated Macrophages (TAMs) are abundantly present at the TME and actively promote
cancer cell proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Active research of the last decade has provided novel therapeutic approaches aimed at depleting TAMs and/or at reprogramming their functional activities. We reported some years ago that the registered anti-
tumor agent
trabectedin and its analogue
lurbinectedin have numerous mechanisms of action that also involve direct effects on immune cells, opening up new interesting points of view.
Trabectedin and
lurbinectedin share the unique feature of being able to simultaneously kill
cancer cells and to affect several features of the TME, most notably by inducing the rapid and selective apoptosis of monocytes and macrophages, and by inhibiting the transcription of several inflammatory mediators. Furthermore, depletion of TAMs alleviates the immunosuppressive milieu and rescues T cell functional activities, thus enhancing the anti-
tumor response to
immunotherapy with checkpoint inhibitors. In view of the growing interest in
tumor-infiltrating immune cells, the availability of
antineoplastic compounds showing immunomodulatory effects on innate and adaptive immunity deserves particular attention in the oncology field.