We revealed 16 immune cell types involving the four immunological signal types (MFI, RC, AC, and MP) in our MR study that are associated with BCa risk, mainly B cell, TBNK cell, Myeloid cell, Treg cell, Maturation stages of T cell, cDC cell.
Our results demonstrated a favorable correlation between the development of BCa and 6 immunocyte morphologies. Among them, CD33br HLA DR+ CD14- %CD33br HLA DR+, CD8br %T cell, HLA DR+ T cell% T cell, HLA DR+ CD4+ AC, CD28 on CD28+ CD4+, CD28 on CD39+ resting Treg,CD8br %T cell, HLA DR+ T cell% T cell, HLA DR+ CD4+ AC,CD11b on CD33br HLA DR+ CD14dim. have also not been studied directly on BCa. However, CD25 is a part of the interleukin-2 (IL-2) receptor and was discovered on the surface of both immune and non-immune cells[26]. CD25 is extensively expressed on regulatory T cells (Tregs), which are known to accelerate the growth of tumors. Research has demonstrated that anti-CD25 antibodies can reduce Treg counts, which can have an anti-tumor immunological impact. Wojciech et al. demonstrated that Regulatory T cells (Tregs; CD4+CD25+FoxP3+) promote immunological tolerance and contribute in the development of BCa, and discovered Treg frequencies throughout the latter stages of tumor growth, which are linked to a reduced anti-tumor response, are a novel and significant prognostic factor in BCa[27]. IgD+ B cells are a subpopulation of B cells that express IgD on their surface to initiate immunological responses. IgD and other immunoglobulins can coexist on B cells and together control immunological responses[28, 29]. Not only may CD4+ T cells transform myeloid cells into IFNγ-induced antigen-presenting cells, but they can also reprogramme them into tumoricidal effectors that express iNOS and can eliminate tumors that evade the immune system[30]. Exhaustion of cytotoxic CD4+ T cells and CD8+ T cells is one of the mechanisms behind tumor immune evasion[31]. Therefore, the findings of the research that point to a mechanistically plausible positive link among the development of BCa and CM CD4+ AC and CD4/CD8br. Following Rituximab treatment of patients with B-cell non-Hodgkin's lymphoma, peripheral blood CD19+ and CD20+ B cell counts significantly dropped. Peripheral blood samples revealed a few CD19+ B cells six months after the treatment's conclusion. These cells displayed high amounts of CD38 and CD24 and had a naïve B cell phenotype (IgD+, CD27-). indicating that igD+ B cells may influence the pathophysiology of B-cell non-Hodgkin's lymphoma via specific pathways and constitute a risk factor for B-cell non-Hodgkin's lymphoma. regardless of the lack of research on the impact on BCa[32].
Leonie et al. demonstrated IgD-CD11c+ CD21low and IgD-CD24+ CD21 high B cells were demonstrated to be significantly reduced in a subset of patients who had autoantibody-positive Neurologic immune-related adverse events (irAE-n). indicating that igD- B cells may influence the pathophysiology of irAE-n via specific pathways and constitute a protective factor for irAE-n. And, the findings of the research that point to a mechanistically plausible negative link among the development of BCa and IgD- CD24- %B cell, CD19 on IgD- CD24- and CD19 on IgD- CD27-[33]. DCs are essential when it comes to inducing the adaptive immune response. They change the direction of T helper responses' polarization and initiation. It is not surprising that changed Dendritic cells (DC) profiles, a subset of antigen-presenting cells (APCs), play a part in the development of autoimmunity. These profiles include migration, tissue distribution, phagocytosis, antigen presentation, and cytokine release[34, 35]. Treatment for vaccines have emerged as a promising treatment strategy for cancer immunotherapy in recent times. Zhang et al. described a vaccination approach based on dendritic cells that might inhibit the development of bladder tumors in vivo and boost the effectiveness of chemotherapy. Moreover, they also examined the in vivo anticancer effects of mature DCs elicited by antigen loading in bladder tumors[36]. This MR analysis also offers evidence that CD62L- monocyte AC, CD62L- HLA DR++ monocyte AC and SSC-A on plasmacytoid DC of cDC team is negatively correlated with the development of BCa. A cell adhesion molecule called CD62L, sometimes referred to as L-selectin, binds to ligands on endothelial cells to engage in leukocyte rolling, adhesion, and migration[37]. Increased CD62L expression enhances the anti-tumor inflammatory response by increasing dendritic cells' capacity to chemoattract. The therapeutic importance of plasmacytoid dendritic cells(pDC), which are multifunctional immune cells, in the tumor microenvironment (TIME) is yet unknown[20]. While, Masanori et al. discovered that high pDC triple negative breast cancer (TNBC) were linked to high expression levels of all immunological check point markers analyzed as well as a large proportion of anti-cancer immune cells. In a word, there was a stronger correlation between pDC levels and immune cell infiltration as well as patient survival in TNBC compared to conventional dendritic cells(cDC)[38]. Previous studies have investigated the impact of CD11b on CD33br HLA DR+ CD14dim. on the risk of PD. While, the idea that CD11b on CD33br HLA DR+ CD14dim. and BCa are correlated is not yet supported by experimental evidence. This discovery opens up new experimental possibilities for studying the connection between BCa and Myeloid cell.
Our study's strengths are that it is the first to use MR methods to look into the connection between immune cell morphologies and BCa. Our findings were obtained by closely examining horizontal pleiotropy, which lessened the influence of reverse causality and confounding variables on the outcomes. Furthermore, immune cell morphologies that have not been as well studied in the past but are strongly linked to BCa were also found in our investigation. This might offer fresh perspectives on possible targets for immunotherapy in BCa. There are several further restrictions on our investigation. Despite the fact that our study includes 731 immune cell morphologies, data restrictions prevented us from analyzing some immune cell phenotypes. Moreover, the fact that the data sources are adult-only, primarily of European heritage, and do not allow for gender or age-based stratification may have an effect on how accurate and broadly applicable the findings are. Using a low threshold value (p < 1.0 × 10−5) when selecting tool variables might result in false positives or miss significant genetic variants associated with immune cell characteristics. There is insufficient experimental data to go deeper into and identify the underlying processes behind the limited link that our research has shown between immune cells and the development of prostate cancer. Important issue is the dearth of impartial cohort studies to support the study's conclusions. To further explore our results and look into possible processes, we want to carry out biological tests in the future.