Specialized Pro-Resolving Mediators Mitigate Cancer-Related Inflammation: Role of Tumor-Associated Macrophages and Therapeutic Opportunities

Abstract

Inflammation is a fundamental physiological response orchestrated by innate immune cells to restore tissue homeostasis. Specialized pro-resolving mediators (SPMs) are involved in active resolution of inflammation but when inflammation is incomplete, chronic inflammation creates a favorable environment that fuels carcinogenesis and cancer progression. Conventional cancer therapy also strengthens cancer-related inflammation by inducing massive tumor cell death that activate surrounding immune-infiltrating cells such as tumor-associated macrophages (TAMs). Macrophages are key actors of both inflammation and its active resolution due to their plastic phenotype. In line with this high plasticity, macrophages can be hijacked by cancer cells to support tumor progression and immune escape, or therapy resistance. Impaired resolution of cancer-associated inflammation supported by TAMs may thus reinforces tumor progression. From this perspective, recent evidence suggests that stimulating macrophage’s pro-resolving functions using SPMs can promote inflammation resolution in cancer and improve anticancer treatments. Thus, TAMs’ re-education toward an antitumor phenotype by using SPMs opens a new line of attack in cancer treatment. Here, we review SPMs’ anticancer capacities with special attention regarding their effects on TAMs. We further discuss how this new therapeutic approach could be envisioned in cancer therapy.

Pro-Resolving Factor Administration Limits Cancer Progression by Enhancing Immune Response Against Cancer Cells

“…Also, we observed that the anti-tumor effect of SuperMApo was dependent on existing host immune cell response specific to cancer cells. Myeloid cells, and macrophages even more, are both sentinel cells controlling tissue hemostasis as well as regulators of pro-tumor inflammation due to their plasticity ( 52 , 53 ). Indeed, macrophages have pro- and also anti-tumor properties ( 18 , 52 – 54 ).…”

“…Myeloid cells, and macrophages even more, are both sentinel cells controlling tissue hemostasis as well as regulators of pro-tumor inflammation due to their plasticity ( 52 , 53 ). Indeed, macrophages have pro- and also anti-tumor properties ( 18 , 52 – 54 ). Tumor-associated macrophages (TAM) are associated with a poor prognosis in cancer ( 18 , 25 , 29 , 52 , 53 , 55 , 56 ).…”

“…Indeed, macrophages have pro- and also anti-tumor properties ( 18 , 52 – 54 ). Tumor-associated macrophages (TAM) are associated with a poor prognosis in cancer ( 18 , 25 , 29 , 52 , 53 , 55 , 56 ). TAM controlled circulating cancer cell recruitment to the primary tumors and are involved in the metastatic cascade ( 29 , 53 , 55 , 57 , 58 ).…”

Long noncoding RNA SNHG4: a novel target in human diseases

“…Inflammation is the basic physiological response of the body to external stimuli; it is usually coordinated by immune cells to restore homeostasis [ 110 ]. In ACI, however, hyperactivated microglia produce massive amounts of inflammatory cytokines, causing inflammatory storms and eventually aggravating disease progression [ 111 ].…”

Debris-stimulated tumor growth: a Pandora’s box?

“…In the subthreshold inoculum model, instead of suppressing tumor growth, chemotherapy promoted tumor growth in small or dormant tumors via tumor-promoting debris [ 1 , 3 ]. Similarly, chemotherapy-generated tumor cell “debris” (apoptotic and necrotic cells and cell fragments) promotes cancer progression and metastasis via stimulating an eicosanoid-driven cytokine storm of pro-inflammatory and pro-angiogenic mediators [ 1 , 2 , 14 , 38 , 39 , 57 , 76 ], polarizing tumor-associated macrophages (TAMs) as well as inducing immunosuppression and limiting anti-tumor immunity [ 24 , 77 , 78 ]. Thus, new approaches to stimulate the clearance of tumor cell debris are urgently needed [ 1 , 21 , 40 , 78 – 80 ].…”