On the surfaces of mast cells and basophils, FcRγ constitutes the core component of the high-affinity IgE receptor FcεRI, forming a tetrameric (αβγ₂) complex (14). Upon cross-linking of the receptor by an allergen-IgE complex, the ITAM of FcRγ rapidly recruits spleen tyrosine kinase (SYK), subsequently phosphorylating it. SYK-activated phospholipase Cγ (PLCγ) hydrolyses phosphatidylinositol bisphosphate to generate inositol trisphosphate (IP₃) and diacylglycerol (14,15). IP₃ subsequently induces intracellular calcium mobilization and extracellular calcium influx, triggering the rapid degranulation of stored mediators such as histamine and tryptamine, which are hallmarks of immediate-type allergic reactions (Fig. 2) (14,15). Knockout of the FCER1G gene prevents IgE-induced mast cell activation and allergic responses in mice (16). This research indicated that FcRγ protein stability is critical for its signaling function (16). For instance, the deubiquitinating enzyme USP5 stabilizes FcRγ by specifically removing K48-linked ubiquitin chains, thereby significantly enhancing IgE-induced mast cell activation and allergic inflammation, while inhibiting USP5 attenuates this process (17). This reveals that targeting FcRγ protein stability represents a novel pathway for regulating allergic responses.

Dendritic cells (DCs): Multireceptor-mediated antigen uptake and immune regulation. The function of FcRγ in DCs exhibits greater diversity and regulatory capacity than in mast cells and basophils, contingent upon the reprogramming of signals from the bound receptor complex FcεRI. The FcεRI expressed by DCs typically adopts a trimeric structure lacking the β chain (αγ₂) (14). This structural difference leads to functional reprogramming, shifting from rapid effector responses towards antigen capture and presentation. In allergic diseases such as atopic dermatitis (AD), upregulation of FcεRI on cutaneous DCs enables efficient internalization of allergens upon IgE binding. These DCs then migrate to lymph nodes, primarily initiating T helper (Th)2-type immune responses, which is an important mechanism in conditions such as AD (14).

For CLRs lacking intracellular signaling domains, such as Dectin-2, FcRγ serves as an indispensable signaling partner. Upon recognizing fungal α-mannan, Dectin-2 activates SYK via the ITAM of FcRγ (18,19). This subsequently activates the NF-κB pathway through the CARD9-BCL10-MALT1 junction complex, driving cytokine production (including IL-6 and IL-23) and promoting Th17 differentiation (Fig. 2) (18,19). This is a critical component of antifungal immunity.

Previous research indicates that FcRγ also exerts negative regulatory effects on DCs. For instance, upon binding to Dectin-1 bearing a semi-ITAM, it may attenuate signal output by recruiting phosphatases such as SHP-1 and PTEN (16). This finely tunes DC maturation and cytokine production, preventing excessive inflammation (Fig. 2). This demonstrates that FcRγ in DCs functions not only as a transmitter of activation signals but also as a precise regulator of immune responses.

NK cells: CD16A (FcγRIIIA) signaling and antibody-dependent cytotoxicity. Within NK cells, FcRγ primarily functions as the signal-adaptor subunit for the low-affinity IgG receptor CD16A (FcγRIIIa). Their binding is essential for the stable expression and functional activity of this receptor on the cell surface. Upon NK cell recognition of tumor cells coated with antibodies (namely therapeutic monoclonal antibodies) via CD16A, phosphorylation of the ITAM recruits and activates SYK. Signaling in NK cells predominantly activates the SYK/PI3K-δ/MAPK axis (20). This pathway drives cytoskeletal reorganization as well as polarization and release of cytotoxic granules-a process involving the directed trafficking of perforin- and granzyme-containing vesicles toward the immune synapse - and promotes IFN-γ production, thereby efficiently executing ADCC (Fig. 2) (20). This constitutes a key mechanism underpinning the efficacy of numerous antibody therapeutics. This study indicates that de-fucosylated antibodies, by enhancing CD16A binding, significantly amplify downstream signaling through SYK/PI3K/MAPK and other pathways, thereby enhancing ADCC efficiency (4). Consequently, the functional state of FCER1G directly influences the efficacy of monoclonal antibody-based tumor immunotherapies.

Macrophages: Integrated signaling regulates phagocytosis, polarization and inflammatory balance. The function of FcRγ in macrophages integrates effector and regulatory roles, reflecting their immunological multifunctionality. As a signal-transducing subunit of receptors such as FcγRI (CD64), FcγRγ plays a pivotal role in mediating ADCP. Following immune complex cross-linking of FcγR, SYK activated by FcRγ-ITAM synergistically initiates multiple downstream pathways, including PLCγ, PI3K and MAPK (5). These collectively regulate actin remodeling, phagosome maturation and reactive oxygen species production, which is essential for phagocytosis, thereby efficiently eliminating antibody-coated targets (Fig. 2) (5).

Regarding bidirectional regulation of inflammatory phenotype and function, FcRγ signaling serves as a pivotal node in modulating macrophage polarization and inflammatory homeostasis. For instance, in atherosclerosis models, immune complexes activate FcγR to drive macrophage polarization towards a pro-inflammatory M1-like phenotype (21). This activates the NF-κB pathway, and leads to substantial release of inflammatory mediators such as TNF-α and IL-6, exacerbating plaque instability and vascular inflammation (21). Conversely, FCER1G deficiency predisposes macrophages towards an anti-inflammatory M2-like phenotype, mitigating disease progression (21). This demonstrates the pivotal role of FcRγ in determining macrophage functional output.

Other cell types and functions. FcRγ also participates in other immune processes, such as acting as a co-signaling chain for the collagen receptor GPVI in platelets to mediate thrombosis, and stabilizing cell surface receptors in type 3 innate lymphoid cells (ILC3s) to promote IL-22 production to combat infections (22,23). Its extensive involvement further underscores its importance as a universal ITAM-binding adaptor protein. FcRγ also functions as a signaling partner for myeloid receptors such as OSCAR and TREM-1, playing roles in several processes such as osteoclast differentiation and inflammatory amplification (24,25).

Despite varying functions across different cell types, the molecular mechanisms initiating FcRγ signaling remain highly conserved. Ligand-induced receptor clustering leads to mutual phosphorylation and activation of adjacent Src family kinases, which subsequently phosphorylate two tyrosine residues on the FcRγ-ITAM. The doubly phosphorylated ITAM recruits and activates SYK with high affinity, establishing SYK as the central hub for downstream signal differentiation (13,26).

From SYK, signals diverge into at least three primary pathways, with cells selectively amplifying specific pathways according to their functional predisposition: i) The PLCγ/Ca²⁺ pathway, which drives rapid degranulation responses in effector cells such as mast cells; ii) the PI3K/MAPK pathway, which predominantly governs ADCC/ADCP, cell migration, cell proliferation, and partial cytokine synthesis in NK cells and macrophages; and iii) the CARD9/NF-κB pathway, which predominantly governs transcriptional activation of pro-inflammatory cytokines and chemokines in DCs, macrophages and other cells following pathogen recognition via CLRs.

Therefore, FcRγ functions as a universal signaling molecule, receiving initial signals from upstream receptor clusters via its ITAM module and subsequently diverting these signals through SYK. Its ultimate functional output is co-programmed by the specific receptor it binds to and the downstream signaling network preferences dictated by the host cell type. This characteristic of ‘common mechanism, differential programming’ provides the molecular basis for understanding how FcRγ serves distinct roles across diverse pathological contexts, including allergy, infection, autoimmunity and even tumorigenesis, while also offering a logical explanation for its paradoxical dual function within the TME.

In anti-infection immunity, the FcRγ exhibits a dual function, with its presence or absence influencing pathogen clearance and host prognosis differently across various infection models, thus profoundly demonstrating its context-dependent nature. In a chronic lymphocytic choroid plexus meningitis virus infection model, FcRγ expressed in NK cells delays pathogen clearance by suppressing virus-specific CD8⁺ T-cell responses (6). In addition, deletion of FcRγ significantly reduces mortality in mouse models of sepsis induced by lipopolysaccharide or Escherichia coli, which is characterized by lower serum levels of TNF-α, IL-6 and IL-10(39). These models suggest that, under certain circumstances, FcRγ-mediated signaling may prove detrimental to infection control or host survival by promoting excessive inflammation or suppressing adaptive immunity. However, in other infection models, FcRγ plays an indispensable role in defensive mechanisms. Conversely, the absence of FcRγ in ILC3s impairs JAK-STAT pathway activation and reduces IL-22 and IL-17A secretion, thereby increasing mortality during fungal infection (22). Similarly, during Pneumocystis pneumonia, FcRγ deficiency decreases the production of inflammatory cytokines (TNF-α, IL-6 and IL-1β) but compromises pathogen clearance efficiency (40). This indicates that FcRγ-mediated immune responses are essential for the effective clearance of the aforementioned pathogens.

The dual outcomes of FcRγ during infection (beneficial or detrimental) are likely determined by two major factors. On the one hand, the type of pathogen and the nature of the infection are critical. For intracellular chronic viruses (such as lymphocytic choriomeningitis virus) or systemic bacterial toxins (sepsis), excessive inflammation or inappropriate immune regulation may lead to immunopathology or tissue damage, where FcRγ activity often contributes to detrimental outcomes. Conversely, combating certain fungi and opportunistic pathogens (such as Pneumocystis) necessitates FcRγ-dependent rapid initiation of innate immune effector programs in specific cells (namely ILC3s), where its function is beneficial. On the other hand, maybe the dominant immune cells and effector mechanisms govern the response. FcRγ's function is entirely dependent on its cellular environment. In NK cells, it may modulate immune crosstalk, occasionally suppressing T cell function, whereas, in ILC3s, it directly stimulates antimicrobial cytokine production. Thus, the cell type dictates whether FcRγ-mediated signaling leads to inhibitory regulation or effector activation.

In summary, the presence of FcRγ is not inherently positive or negative in infectious immunity. Instead, its value depends on the immune equilibrium set by the specific infection microenvironment. FcRγ dynamically modulates the intensity and quality of immune responses by influencing two critical balances: i) Pro-inflammation vs. anti-inflammation and ii) immune activation vs. suppression. This capacity for flexible role-switching in response to microenvironmental signals and precise regulation of immune balance bears striking similarity to the functional plasticity of immune checkpoint molecules within the TME, and provides a core logical framework for understanding the complex role of FCER1G in tumor immunity.

Pan-cancer analysis based on the TIMER 2.0 database (https://compbio.cn/timer2/) shows that FCER1G is significantly upregulated in 9 types of malignant tumor compared with normal tissues (Fig. 4). These include esophageal carcinoma, glioblastoma multiforme (GBM), head and neck squamous cell carcinoma, kidney clear cell carcinoma, kidney papillary cell carcinoma, stomach adenocarcinoma (STAD) and thyroid carcinoma. Gene enrichment analyses further reveal that FCER1G is predominantly involved in cell proliferation-related pathways across multiple tumor types, particularly STAD, TGCT, acute myeloid leukemia and GBM (P<0.05, false discovery rate <0.25) (41). Furthermore, FCER1G expression positively correlates with >50% of immune checkpoint genes, suggesting that it functions as a hub regulator within the tumor immunoregulatory network (41). Single-cell transcriptomic data from the TISCH database indicate that FCER1G is preferentially expressed in monocyte/macrophage populations within the TME across ~85% of the tumors analyzed, thus providing cellular-level evidence for its involvement in TME remodeling.

Comprehensive analysis indicates that FCER1G is highly expressed in multiple solid tumors, including clear cell renal cell carcinoma (ccRCC) (presented as KIRC in Fig. 4), esophageal squamous cell carcinoma (ESCC) (included within the esophageal cancer group when presented in Fig. 4) and STAD (7,8,42) (Fig. 4). Its expression is predominantly enriched in myeloid immune cells, where it promotes the formation of an immunosuppressive microenvironment, thereby contributing to poor prognosis.

Data from the Human Protein Atlas (HPA) show markedly stronger immunohistochemical staining of FCER1G in renal carcinoma tissues than in adjacent normal tissues (Fig. 5). According to Wang et al (7), analysis of the ONCOMINE database and three validation datasets identified significantly elevated FCER1G expression in ccRCC, where high expression correlated with reduced overall survival (OS). Similarly, Dong et al (43) observed that, in ccRCC, FCER1G expression exhibited a strong correlation with CD68 and co-localization with macrophages. Their concurrent overexpression portends an unfavorable prognosis. Joint assessment of FCER1G and CD68 expression levels can optimize prognostic stratification models for patients. Furthermore, gene set enrichment analysis revealed that high FCER1G expression is associated with suppression of T-cell activation and proliferation (43). FCER1G shows moderate diagnostic accuracy (area under the curve, 0.74) in distinguishing localized (stage I/II) from advanced (stage III/IV) ccRCC, and functions as an independent prognostic biomarker (44).

In ESCC, FCER1G is predominantly enriched within the tumor stroma. Double immunofluorescence staining clearly demonstrates that FCER1G-positive cells highly co-express the M2 macrophage marker CD163, meaning that the majority of infiltrating M2 macrophages simultaneously express FCER1G (42). The infiltration density of these FCER1G⁺ M2 macrophages correlates directly with worse prognosis, and FCER1G itself constitutes an independent risk factor affecting patients' OS (42). In STAD, analyses from multiple transcriptomic cohorts (The Cancer Genome Atlas, GSE13195 and GSE15459) consistently showed higher FCER1G expression in tumor tissues than in adjacent normal tissues (8,41,45). Its overexpression is linked to poorer OS and increased infiltration of M2 macrophages (8). Furthermore, FCER1G expression progressively increases with advancing tumor stage, suggesting a dynamic upregulation trend during tumor progression. This finding, similar to that observed for ESCC, suggests that FCER1G may be primarily expressed in M2-type tumor-associated macrophages (TAMs) within STAD and participate in shaping the immunosuppressive microenvironment.

Additionally, in gliomas, diffuse large B-cell lymphoma, bladder cancer and papillary thyroid carcinoma, FCER1G acts as a progression-associated gene, where high expression of FCER1G correlates with aggressive tumor behavior, poor prognosis and distinct immune infiltration patterns (11,46-51). In osteosarcoma, a dual-gene risk model incorporating FCER1G and SPI1, developed based on Cox regression analysis, holds independent prognostic significance. Patients in the low-expression group for this signature exhibit an immunosuppressive microenvironment, worse clinical outcomes and a higher risk of metastasis, highlighting the potential of FCER1G as a prognostic biomarker and immunotherapeutic target (52). It is noteworthy that bioinformatics analysis suggests that FCER1G may be a hypermethylated gene in osteosarcoma, offering a potential epigenetic hypothesis to explain its low expression in this tumor type. However, the precise regulatory mechanisms require experimental validation (35).

In summary, FCER1G is highly expressed in multiple solid tumors, including ccRCC, ESCC, STAD and glioma. By promoting M2 macrophage infiltration and shaping an immunosuppressive TME, it contributes to tumor progression and serves as a consistent indicator of poor prognosis across various cancer types (Table I).

FCER1G correlates with favorable patient prognosis. In contrast to its generally pro-tumor pattern, FCER1G displays a protective role in certain malignancies, where high expression is associated with prolonged survival and enhanced immune activation. In MM, analyses of several datasets (including GSE39754, GSE5900 and GSE2113) reveal a progressive decline in FCER1G expression with disease advancement (9,53). Multivariate Cox regression analysis identifies high FCER1G expression as an independent predictor of both event-free survival and OS, establishing it as a favorable prognostic biomarker in MM (9). Furthermore, FCER1G overexpression correlates with NK cell-mediated cytotoxic pathways (9). Notably, previous research has identified a functionally distinct FcεRIγ^- NK cell subset (termed g-NK cells) (54). Compared to conventional NK cells, these cells exhibit enhanced ADCC following CD16 cross-linking and significantly amplify the efficacy of monoclonal antibodies such as daratumumab in preclinical models (54). This offers a novel perspective on the association between FCER1G expression in MM, NK cell function and favorable prognosis. Similarly, in uterine corpus endometrial carcinoma (UCEC), high FCER1G expression predicts improved prognosis, and correlates with increased infiltration of immune cells, including B cells, CD8⁺ T cells and DCs (Table I) (10).

In lung adenocarcinoma (LUAD), FCER1G expression exhibits stage-specific dynamics, being downregulated in early stages and restored at advanced stages (55). Network analyses further indicate that FCER1G consistently functions as an immune regulatory hub throughout LUAD progression, and that its functional loss impairs antitumor immune activity (55).

Overall, the prognostic significance of FCER1G shows clear tumor-type specificity.

In malignancies such as MM and UCEC, as well as in specific stages of LUAD, elevated FCER1G expression is not associated with tumor promotion. Instead, it may exert a protective effect by sustaining or activating antitumor immune responses, ultimately predicting more favorable clinical outcomes (Table I).

Contradictory prognostic value of FCER1G arises from heterogeneity in the TME. In summary, the prognostic value of FCER1G exhibits marked inconsistencies, fundamentally stemming from the cellular types expressing FCER1G, which determine the nature of the specific, coordinated immune processes in which it participates (Fig. 6).

Regarding its expression in immunosuppressive myeloid cells (pro-tumor function), in solid tumors such as ccRCC and ESCC, FCER1G is primarily expressed in M2-type TAMs. These cells shape an immunosuppressive TME by secreting immunosuppressive factors (such as IL-10 and TGF-β), depleting T cells and promoting angiogenesis. This drives tumor progression and immune evasion, leading to poor prognosis (42,43). Regarding its expression in cytotoxic cells or APCs (antitumor function), in tumors such as MM and UCEC, high expression of FCER1G correlates with the active state of effector cells or APCs, including DC, and NK, cytotoxic T and B cells. In this context, FCER1G functions as a signaling adaptor for activation receptors (CD16A) on these cells, participating in the initiation of antitumor immune responses such as ADCC and T-cell activation, thereby correlating with favorable prognosis (9,10,41).

Therefore, assessing the clinical relevance of FCER1G necessitates moving beyond mere expression levels to deeply analyze its cellular localization and the associated functional state of the overall immune microenvironment. This cellular context determinism lies at the core of understanding its complexity as a biomarker.

FCER1G exhibits distinct immunoregulatory patterns across different tumor types. In STAD, its expression correlates positively with the infiltration of M1/M2 macrophages, quiescent mast cells and DCs, but negatively with plasma and CD8⁺ T cells (45). This opposing infiltration pattern indicates that FCER1G may facilitate tumor progression by reshaping an immunosuppressive immune microenvironment. In glioma, FCER1G expression is strongly associated with the infiltration of T cells, macrophages and B cells, further implicating it in disease progression and immune landscape remodeling (47). Notably, previous single-cell RNA sequencing studies have identified a tumor-specific, innate-like cytotoxic T-cell subset characterized by FCER1G⁺ αβTCR⁺ cells (56,57). FCER1G serves as a definitive lineage marker for this population. Unlike conventional tumor-reactive T cells, these cells recognize unmutated self-antigens presented by MHC-I molecules rather than tumor-derived neoantigens. Their intratumoral activation and effector functions depend strictly on the IL-15 signaling axis, underscoring a unique FCER1G-mediated mechanism of cytotoxic immune regulation within the TME (56,57).

This identification implies that FCER1G is not merely a participant in immunosuppression but also acts as a phenotypic identity tag for specific antitumor immune cell subsets, highlighting its multifaceted roles within the TME. Collectively, the evidence suggests that FCER1G possesses dual regulatory properties. It can promote immunosuppressive phenotypes in certain contexts while also functioning as a key regulatory node for antitumor responses in distinct immune populations. Dysregulation of its expression or signaling may therefore disrupt immune homeostasis and drive the pathological remodeling of the TME.

Supporting its functional relevance, analyses of the Gene Expression Profiling Interactive Analysis and HPA databases showed that FCER1G expression is significantly higher in PAAD tissues than in normal tissues at both the mRNA and protein levels. In animal models, FcRγ-deficient [FCER1G^-/^-, FcRγ knockout (KO)] mice bearing pancreatic ductal adenocarcinoma exhibit reduced tumor growth and attenuated desmoplasia, accompanied by a complete loss of FcγRI/III expression within tumors (58). These findings indicate that FCER1G likely modulates the TME and drives malignant progression through the regulation of Fc receptor-mediated signaling pathways.

Promotion of angiogenesis. Andreu et al (59), using an HPV16⁺/FcRγ^-/^- mouse model, revealed a key role for FcRγ in tumorigenesis. Compared with wild-type (WT) mice, FcRγ KO mice showed a lower incidence of SCC. This effect was associated with inhibited angiogenesis and decreased expression of major oncogenic factors, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) (59). Further experiments demonstrated that mast cells and macrophages promote endothelial cell migration via FcRγ-dependent pathways, thereby enhancing the in vivo tumorigenicity of the PDSC5 SCC cell line (59). Collectively, these findings indicate that FcRγ promotes tumor angiogenesis by mediating interactions between immune and stromal cells within the TME.

Promotion of tumor metastasis. The expression status of FCER1G is frequently implicated in tumor metastasis, although its effects vary among cancer types. In hepatocellular carcinoma (HCC), FCER1G shows a downregulated trend, and its low expression is associated with the activation of apoptotic and ferroptotic pathways (60). Previous in vitro experiments have shown that silencing FCER1G enhances the proliferation and migration of HCC cells by upregulating Snail1, TWIST1 and N-cadherin while suppressing E-cadherin expression (60). These results suggest that FCER1G may restrain HCC invasiveness by modulating epithelial-mesenchymal transition (EMT) processes.

In malignant melanoma (MEL), the role of FcRγ exhibits a more intricate profile, characterized by context-dependent effects. On the one hand, lung metastasis can be suppressed by treatment with the monoclonal antibody TA99 or intravenous Ig (IVIG) (61,62). This antimetastatic effect depends entirely on FcRγ, as it is abolished in FcRγ KO mice, indicating that ADCC serves as a key mechanism. On the other hand, FcRγ deficiency itself exerts dual and opposing effects on metastasis (Fig. 7). Specifically, the absence of FcRγ enhances platelet adhesion to circulating tumor cells, and stimulates platelets to release the chemokines C-X-C motif chemokine ligand (CXCL)5 and CXCL7. This cascade promotes neutrophil recruitment to lung tissue and creates a pro-transfer microenvironment that accelerates lung metastasis without affecting primary tumor growth (3).

Furthermore, FcRγ KO impairs CD244-mediated inhibitory signaling during NK cell development, leading to diminished NK cell function (63). This defect can be reversed by treatment with IL-2 or IL-15, which upregulates activation receptors [natural killer cell group 2 (NKG2)D and DNAX accessory molecule-1] and downregulates inhibitory receptors (LY49 and NKG2A), thereby restoring NK cell cytotoxicity and suppressing metastasis (63). Therefore, therapeutic strategies aimed at modulating FcRγ signaling must carefully balance the benefits of enhancing antibody-dependent tumor clearance against the potential risk of facilitating metastatic dissemination.

FcRγ serves as a critical molecular determinant for the efficacy of multiple antibody-based therapies. In colorectal cancer (CRC), FCER1G expression is paradoxically higher in adjacent non-tumorous tissues than in tumor tissues (64). Within this setting, IVIG treatment fails to produce antitumor effects in FcRγ KO mice. Mechanistically, the therapeutic activity of IVIG depends on FcγRI/III signaling, which drives the reprogramming of TAMs from an M2-like, pro-tumor state toward an M1-like, antitumor phenotype (64).

In adult T-cell leukemia/lymphoma (ATL) models, anti-CD2 monoclonal antibody MEDI-507 and anti-CD25 monoclonal antibodies significantly suppress tumor progression and prolong survival, with their efficacy strictly dependent on FcRγ (65,66). Specifically, polymorphonuclear leukocytes and monocytes eliminate CD2⁺/CD25⁺ tumor cells through FcγRIII-mediated ADCC (65,66). The absence of FcRγ disrupts this pathway, resulting in therapeutic resistance despite normal antibody pharmacokinetics.

It is noteworthy that not all antibody therapies rely on FcγR signaling. In anaplastic large-cell lymphoma (ALCL), the anti-CD30 monoclonal antibody HeFi-1 suppresses tumor growth primarily by inducing G₁-phase cell-cycle arrest, thereby exerting its antitumor effect independently of FcγRIII expression (67).

In general, these findings underscore a crucial principle: For a broad range of antibody therapies targeting tumors such as CRC and ATL, the FcγRI/III signaling pathway represents an indispensable axis for antitumor efficacy. This pathway mediates the key effector functions of myeloid cells, including macrophages and neutrophils, in achieving therapeutic success.

Impact of drug intervention on the prognostic value of FCER1G. The prognostic importance of FCER1G in ccRCC appears to be treatment specific. It shows strong prognostic value in patients treated with the anti-PD-1 antibody nivolumab, but not in those receiving the mTOR inhibitor everolimus (43). This treatment-specific difference may reflect the regulatory role of FCER1G in modulating responses to immune checkpoint inhibitors such as nivolumab, whereas its association with mTOR pathway-targeted therapies appears to be relatively weak (41). Furthermore, pharmacological interventions can dynamically influence the immunoregulatory activity of FcRγ. For instance, peripheral blood NK cells from lung transplant recipients treated with rapamycin (an mTOR inhibitor) exhibit markedly reduced FcRγ expression. This observation suggests that drug-induced modulation of FcRγ may indirectly affect immune homeostasis and therapeutic outcomes (68).