The neonatal Fc receptor in cancer FcRn in cancer

Abstract

Since the neonatal IgG Fc receptor (FcRn) was discovered, it was found to be involved in immunoglobulin recycling and biodistribution, immune complexes routing, antigen presentation, humoral immune response, and cancer immunosurveillance. The latest data show that FcRn plays a part in cancer pathophysiology. In various types of cancers, such as lung and colorectal cancer, FcRn has been described as an early marker for prognosis. Dysregulation of FcRn expression by cancer cells allows them to increase their metabolism, and this process could be exploited for passive targeting of cytotoxic drugs. However, the roles of this receptor depend on whether the studied cell population is the tumor tissue or the infiltrating cells, bringing forward the need for further studies.

Neonatal Fc receptor expression in lymphoid and myeloid cells in systemic lupus erythematosus

“…8 The pathophysiological role of FcRn has emerged in cancer after the discovery of relationships between its low expression level and tumor size or bad prognosis in patients. [8][9][10] Other data suggest that FcRn is also involved in the pathophysiology of antibody-mediated autoimmune diseases. FcRn-dependent antibody transcytosis and IC crosspresentation appear to be involved in autoimmune-mediated glomerulonephritis, as suggested by Olaru et al 11 in mouse models using wild-type, FcRn-knocked-out-, or -humanized C57Bl/6 mice immunized with the non-collagenous domain of the α3 chain of type IV collagen.…”

The Neonatal Fc Receptor Is Elevated in Monocyte-Derived Immune Cells in Pancreatic Cancer

“…It has been hypothesized that this lack of efficacy may be due to the observations that PDAC patients are highly immunosuppressed with low T cell tumor infiltration and low tumor mutation burden, leading to lower neoantigen potential [27,28]. As previously noted, FcRn is integral to the processing and presentation of antigens within APCs [4,20,42,43]. If FcRn is unable to deliver its IgG payload to the appropriate destination, it cannot be properly processed and loaded onto the MHC for T cell presentation, and a dampened T cell response may result.…”

“…However, to our knowledge, systemic changes in FcRn expression within these critical cell types in disease states have not been studied. Furthermore, studies on disease-related changes in FcRn that do exist focus exclusively on expression and activity intrinsic to disease tissue, such as tumor cells [20][21][22][23][24]. Taken together, these gaps in knowledge support a broader characterization of FcRn in systemic immune populations occurring as a function of disease.…”

Antibody–Drug Conjugates as an Emerging Therapy in Oncodermatology

“…While affinity of a mAb for its epitope is determined by the Fab portion [10], the Fc part is determinant for mAb stability and interactions with immune cells such as antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated phagocytosis (ADCP). To this end, the Fc part interacts with neonatal Fc receptor (FcRn) [23], a recycling receptor determining both IgG half-life and biodistribution [24], or complement (C1q) implied in CDC or Fc receptors on immune effector cells (FcγR), a family of receptors which may trigger an immune response upon Fc binding [25]. The ADC interactions with immune cells might either constitute an opportunity to induce an antitumor response, or represent a potential side effect, resulting in toxicity on immune cells [14].…”