Abstract
Cancers are consequences of cellular dysfunction leading to an aberrant cellular multiplication and proliferation, subsequently yielding metastasis formation. Inflammatory reaction, with immune cell recruitment, is the main defense against precancerous lesions. However, an inflammatory environment also favors cancer cell progression, with cancer cell evasion from immune surveillance, leading to cancer development. Current therapeutic strategies enhance this natural immune response in order to restore immunosurveillance. The variety of these strategies is a predominant source of inflammatory mediators used by cancer cells to grow, differentiate, and migrate, therefore encouraging metastasis formation. For this reason, during cancer progression, limiting inflammation appears to be an innovative strategy to avoid the escape of cancer cells and potentially enhance the efficacy of antitumor therapies. Thus, this study aims to investigate the impact of administering pro-resolving factors (SuperMApo® drug candidate), which are inducers of inflammation resolution, in the framework of cancer treatment. We have observed that administering pro-resolving mediators issued from apoptotic cell efferocytosis by macrophages controlled peritoneal cancer progression by limiting cancer cell dissemination to the blood and mesenteric lymph nodes. This observation has been linked to an increase of macrophage mobilization in both peritoneal cavity and mesenteric lymph nodes. This control is associated to a restricted immunosuppressive myeloid cell circulation and to an IFN-γ-specific anti-tumor T-cell response. Altogether, these results suggest that administering proresolving factors could provide a new additional therapeutic alternative to control cancer progression.
Highlights
Inflammation is a natural process of the body to fight against aggressions such as infections and against cancer cells
In an experimental model of peritoneal cancer induced in C57Bl/ 6 mice injected with EL4 cancer cells into the peritoneal cavity, we evaluated the administration of pro-resolving factors (SuperMApo) at the time of cancer detection by luminescence
We observed a reduced cancer progression compared with the mice receiving vehicle for the 2 weeks, as attested by a reduced radiance observed in mice treated with SuperMApo versus control (Figures 1A–C)
Summary
Inflammation is a natural process of the body to fight against aggressions such as infections and against cancer cells. In addition to a lipid switch from pro-inflammatory lipid production to specialized proresolutive lipid mediators (SPM) synthesis, apoptotic cellderived factors and the factors released by phagocytes eliminating apoptotic cells initiate the resolution process. This limits innate cell infiltration, enhances efferocytosis, and favors return to homeostasis. Resident cells (macrophages and dendritic cells) react to tumor antigens and initiate inflammation by secreting proinflammatory mediators, such as cytokines (IL-1b, IL-6, TNF-a) [11] This inflammatory microenvironment favors other immune cell recruitment, such as monocytes, which differentiate into inflammatory cells. In the tumor, activated myeloid cells capture tumor-derived antigen and migrate to lymphoid organs in order to present the antigen and stimulate T cells, enhancing adaptive immunity against cancer cells, and kill them at the tumor site [12,13,14,15]
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