Macrophages and dendritic cells (DCs) are important contributors to anti-tumor immune
responses. However, these highly plastic cells are also the primary targets of tumor
manipulation, which may result in the development of tumor-promoting subtypes. The
effect of chemotherapeutic agents on tumor cells is an area of intense study, but
little is known about their effects on innate immune cells.We investigated the effects
of four chemotherapeutic drugs (two platinum-based agents; oxaliplatin and cisplatin,
and two anthracyclines; doxorubicin and epirubicin) on the differentiation, function,
and viability of macrophages and DCs. Macrophages and DCs were differentiated from
monocytes in the presence of these chemotherapeutic drugs and we compared their cell
surface receptor expression, cytokine production, and chemotactic- and T-cell-polarizing
ability.We have shown that differentiation in the presence of anthracyclines dose-dependently
increases CTLA-4 expression in DCs. Antineoplastic agent-driven differentiation strongly
modified the CCL2- or CCL5-induced chemotactic activity of both macrophages and DCs.
DCs differentiated in the presence of high-dose cisplatin and a low dose of epirubicin
promoted regulatory T-cell development, whereas oxaliplatin at specific doses induced
both DCs and macrophages to enhance cytotoxic T-cell responses. Furthermore, we found
that inflammatory macrophages are more sensitive to doxorubicin-induced cell death
than their counterparts.In summary, our results confirm that chemotherapeutic agents
acting on a similar basis may have different effects on the anti-tumor immune response.
Treatment with optimal dose, combinations, and timing of chemotherapy may determine
tumor immunity and the metastatic potential of tumors.
