Relevance of Fc Gamma Receptor Polymorphisms in Cancer Therapy With Monoclonal Antibodies

Therapeutic monoclonal antibodies (mAbs), including immune checkpoint inhibitors (ICIs), are an important breakthrough for the treatment of cancer and have dramatically changed clinical outcomes in a wide variety of tumours. However, clinical response varies among patients receiving mAb-based treatment, so it is necessary to search for predictive biomarkers of response to identify the patients who will derive the greatest therapeutic benefit. The interaction of mAbs with Fc gamma receptors (Fc gamma R) expressed by innate immune cells is essential for antibody-dependent cellular cytotoxicity (ADCC) and this binding is often critical for their in vivo efficacy. Fc gamma RIIa (H131R) and Fc gamma RIIIa (V158F) polymorphisms have been reported to correlate with response to therapeutic mAbs. These polymorphisms play a major role in the affinity of mAb receptors and, therefore, can exert a profound impact on antitumor response in these therapies. Furthermore, recent reports have revealed potential mechanisms of ICIs to modulate myeloid subset composition within the tumour microenvironment through Fc gamma R-binding, optimizing their anti-tumour activity. The purpose of this review is to highlight the clinical contribution of Fc gamma R polymorphisms to predict response to mAbs in cancer patients

Effects of Spaceflight on the Immune System

The immune system belongs to the most affected systems during spaceflight, and sensitivity of cells of the human immune system to reduced gravity has been confirmed in numerous studies in real and simulated microgravity. Immune system dysfunction during spaceflight represents a substantial risk for exploration class mission knowledge about the clinical, cellular, and genetic basis of immune system response, and adaptation to altered gravity will provide key information for appropriate risk management, efficient monitoring, and countermeasures against existing limiting factors for human health and performance during manned exploration of the solar system. In spite of the immune system dysregulation, studies indicate an adaptation reaction of the immune system to the new microgravity environment, at least for the T-cell system, starting after 2 weeks and continuing until 6 months or longer, reflected by cytokine concentrations in blood plasma or in stimulation assays. At the cellular level, rapid adaptation responses could be detected as early as after seconds until minutes in T cells and macrophages. Therefore, adaptive responses of cells and the whole organism could be expected under microgravity and altered gravity in general. Preventive countermeasures should therefore consider support and stabilization of the endogenous adaptation programs. Potential countermeasures for risk mitigation are summarized in this chapter. We assume that the immune systems not only have a significant adaptation potential when challenged with low gravitational environments but also provide interesting preventive and therapeutic options for long-term space missions