Old and New Players of Inflammation and Their Relationship With Cancer Development

Abstract

Pathogens or genotoxic agents continuously affect the human body. Acute inflammatory reaction induced by a non-sterile or sterile environment is triggered for the efficient elimination of insults that caused the damage. According to the insult, pathogen-associated molecular patterns, damage-associated molecular patterns, and homeostasis-altering molecular processes are released to facilitate the arrival of tissue resident and circulating cells to the injured zone to promote harmful agent elimination and tissue regeneration. However, when inflammation is maintained, a chronic phenomenon is induced, in which phagocytic cells release toxic molecules damaging the harmful agent and the surrounding healthy tissues, thereby inducing DNA lesions. In this regard, chronic inflammation has been recognized as a risk factor of cancer development by increasing the genomic instability of transformed cells and by creating an environment containing proliferation signals. Based on the cancer immunoediting concept, a rigorous and regulated inflammation process triggers participation of innate and adaptive immune responses for efficient elimination of transformed cells. When immune response does not eliminate all transformed cells, an equilibrium phase is induced. Therefore, excessive inflammation amplifies local damage caused by the continuous arrival of inflammatory/immune cells. To regulate the overstimulation of inflammatory/immune cells, a network of mechanisms that inhibit or block the cell overactivity must be activated. Transformed cells may take advantage of this process to proliferate and gradually grow until they become preponderant over the immune cells, preserving, increasing, or creating a microenvironment to evade the host immune response. In this microenvironment, tumor cells resist the attack of the effector immune cells or instruct them to sustain tumor growth and development until its clinical consequences. With tumor development, evolving, complex, and overlapping microenvironments are arising. Therefore, a deeper knowledge of cytokine, immune, and tumor cell interactions and their role in the intricated process will impact the combination of current or forthcoming therapies.

Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment

“…On the other hand, it has been shown that chronic inflammation caused by an incomplete resolution process favors tumor progression. Excellent reviews have been published on the dual role of the immune system in tumor biology ( 10 – 12 ).…”

From reactive species to disease development: Effect of oxidants and antioxidants on the cellular biomarkers

“…However, deregulation of inflammation can exacerbate the original damage and lead to acute or chronic inflammatory disease. [ 68 ] In this case, NF‐κβ factor acts as a central mediator in the induction of proinflammatory genes and induces the activation of both innate and adaptive immune cells in the presence of infection. [ 69 ]…”

The systemic-level repercussions of cancer-associated inflammation mediators produced in the tumor microenvironment

“…From this point of view, NK cell overactivity increases the proportion of dying tumor cells and releases more DAMPs are released, which act as “find me” signals, and tumor antigens. These tumor-released compounds promote the arrival of inflammatory and immune cells, initiating an acute inflammatory process ( 42 , 43 ). In this setting, tissue-resident macrophages, dendritic cells (DCs), and recruited monocyte-derived DCs comprise the mononuclear phagocytic system ( 44 , 45 ), playing a critical role in homeostasis, tissue repair, the immune response, and cancer ( 46 ).…”