Targeting the innate immune system has attracted attention with the development of anti-CD32b antibodies. CD32b (FcγRIIB or FCGR2B) is involved in the phagocytosis of immune complexes and in the regulation of antibody production by B-cells. CD32b has been shown to perform unexpected activatory roles in both immune-signaling and monoclonal antibody (mAb) immunotherapy. Understanding their role and relationship with immune infiltrates is an area of interest in cancer research.
The KM Plotter online Tool (http://www.kmplot.com), a publicly available database, was used to study the relationship between the expression of CD32b gene from the validated immune signatures and patient clinical outcomes for BC. Patients were divided into two groups, high vs. low expression, based on the best cut-off values of gene expression (smallest p-value). The best cut-off values were determined by algorithms embedded in KM plotter. The OS KM plots are present with the hazard ratio (HR), the 95% confidence interval (CI) and log-rank p-value. The Tumor Immune Estimation Resource (TIMER) online tool was used to explore the association between the abundance of tumor immune infiltrates (B-cells, CD4+ T-cells, CD8+ T-cells, dendritic cells, macrophages, and neutrophils) and the expression of CD32b. The correlation graphics show the purity-corrected partial Spearman’s correlation and its statistical significance.
We identified CD32b gene, which predict worse prognosis in HER2+ B luminal BC (OS: HR = 0.48 (0.31 -0.74), logrank P = 0.00083; RFS: 0.77 (0.62 – 0.95), logrank P = 0.016). Their expression positively correlated with the presence of immune infiltrates within the tumor CD4+ T cells (partial.cor =0.393, p = 2.29e-03), neutrophils (partial.cor = 0.476, p = 1.60e-04), CD8+ T cells (partial.cor = 0.285, p = 3.15e-02), dendritic cells (partial.cor = 0.639, p = 6.59e-08), macrophage (partial.cor = 0.639, p = 6.59e-08) and B cells (partial.cor = 0.125, p = 3.50e-01), with markers of T cell activation and antigen presentation.
High expression of CD32b is associated with worse prognosis in HER2+ B luminal BC. CD32b is a target for the future development of novel therapeutics.
The authors.
Cellex Foundation Institutional grant: Research facilities and equipment La Caixa Foundation Institutional grant: LCF/PR/CEO7/50610001.
All authors have declared no conflicts of interest.