Dear Colleagues,

The response of the body to an adverse event or a pathogen follows well-known phases of resistance and tolerance. The cancer cell could be considered as a pathogen and, therefore, its related pathology would depend on the extent of its growth (tumor burden) and the efficiency of the immune system to counteract it. Resistance aims to reduce the burden of the “pathogen”: in this phase, the immune system recognizes the antigenic diversity of the tumor and, as a function of its effectiveness, can eliminate it. Macrophages, dendritic cells, as well as T and B lymphocytes are known to mainly participate in these phases of resistance to tumors, with specific metabolic events useful for the uncontrolled growth of cancer occurring. Thus, the clinical manifestation of the neoplasm highlights the lack of control of the growth of a tumor, its poor immunogenicity, or the reduced effectiveness of the immune system, which can be overcome by the escape mechanisms exerted by the cancer itself. The growth of a tumor that overcomes the mechanisms of resistance underlines the lack of efficacy of the immune system, which is then followed by a chronic inflammatory response exerted mainly by macrophages with related symptoms of “sickness behavior” (anorexia, fatigue, and anemia) exemplify the mechanism of tolerance. Tolerance is a phase that occurs to limit the damage caused by chronic activation of the immune system itself after resistance has failed. Although the resistance strategy might be crucial for the protection of the “host” from cancer, it has also been shown to be accompanied by collateral damage to tissues that negatively impact the fitness of the host leading to so-called immunopathology. Immunopathology is considered an unavoidable consequence of immune defenses. In general, the degree of immunopathology is thought to be positively correlated with the magnitude and duration of the immune response. The optimal immune response might be determined by the balance between the efficient clearance of the pathogen and an acceptable level of tissue damage.

The persistence of cancer and the activation of innate response with an excessive and prolonged aspecific inflammation is no longer a positive event in terms of immunosurveillance and contributes to immunosuppression and is associated with the release of several pro-inflammatory mediators, particularly from macrophages, that lead to dramatic systemic changes and symptoms that can severely damage the host. Then, the mechanism of tolerance known to be a last attempt defense strategy of the “host”, may result in further harm/damage. The transition from the mechanisms of resistance to tolerance helps to explain the onset of the anorexia/cachexia syndrome, which is recognized as one of the main causes of death in most cancer patients.

This Special Issue will collect both reviews and original research that discusses and clarifies the mechanisms of resistance and tolerance that drive the host immune response to cancer, the role of chronic inflammation in such processes and the role of immunopathology, and tolerance in the pathogenesis of cancer-related symptoms.

Sub-topics include the following:

• Immunological mechanisms of antineoplastic resistance
• Role of resistance and tolerance during the course of the neoplastic disease
• Role of macrophages in the evolution of cancer disease
• Cachexia is a mechanism of resistance or tolerance?
• Significance of anorexia
• Significance of anemia
• Role of anticancer treatment against immunopathology

Dr. Antonio Maccio
Guest Editor

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• ovarian cancer
• laparoscopic surgery
• immune system and immunotherapy
• inflammation
• macrophages
• cytokines
• cancer cachexia
• cancer-related anemia