During tissue damage caused by infection or sterile inflammation, not only damage-associated molecular patterns (DAMPs), but also resolution-associated molecular patterns (RAMPs) can be activated. These dying cell-associated factors stimulate immune cells localized in the tissue environment and induce the production of inflammatory mediators or specialized proresolving mediators (SPMs). Within the current prospect of science, apoptotic cell death is considered the main initiator of resolution. However, more RAMPs are likely to be released during necrotic cell death than during apoptosis, similar to what has been observed for DAMPs. The inflammatory potential of many regulated forms of necrotic cell death modalities, such as pyroptosis, necroptosis, ferroptosis, netosis, and parthanatos, have been widely studied in necroinflammation, but their possible role in resolution is less considered. In this review, we aim to summarize the relationship between necrotic cell death and resolution, as well as present the current available data regarding the involvement of certain forms of regulated necrotic cell death in necroresolution.

In addition to killing malignant cells, effective cancer therapies must also promote the development of an immunostimulatory tumor microenvironment (TME). Macrophages are the most abundant immune cell population within the TME. These highly plastic cells play key roles in tumor progression, chronic inflammation, immunosuppression, and metastasis. Although increasing research efforts focus on manipulating macrophage functions, relatively little is known about how standard anticancer strategies, especially chemotherapeutic agents, influence the composition, polarization state, and functional behavior of macrophage subpopulations. Chemotherapeutic agents remain a primary treatment option for many types of cancer, including breast and cervical cancers. In this study, we used epirubicin and doxorubicin at near-therapeutic concentrations and examined their effects on macrophage functions in co-culture with MDA-MB-231 breast cancer and HeLa cervical cancer cell lines. We demonstrated that the presence of tumor cells led to increased expression of the M2 macrophage marker CD206, a change that was reduced by both chemotherapeutic agents. The production of macrophage-derived chemokines, such as IP-10 and IL-8, was also altered by tumor presence and drug exposure. A striking finding was that the co-presence of chemotherapeutic agents and MDA-MB-231 cells synergistically altered macrophage motility. This effect was not observed in monocultures. Furthermore, the presence of tumor cells reduced the susceptibility of pro-inflammatory M1 macrophages to drug-induced cell death. These results indicate that chemotherapy can reshape the macrophage landscape in the TME. We highlight that the combined effects of tumor cell presence and chemotherapy modulate the composition, phenotype, and migration of macrophage subtypes differently than either factor alone.