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Microbes & Immunity The feature of bladder cancer stem cells

(SM), and triacylglycerols (TGs). qRT-PCR and (HLA)-E, which is associated with immune evasion.
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immunoblot assays further substantiated the mesenchymal Given the suppressive role of NKG2A on immune cells,
characteristics of GD2 cells, with decreased E-cadherin it becomes imperative to block the NKG2A-HLA-E axis.
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expression and increased vimentin expression. These Furthermore, the combination of a PD-1 inhibitor with an
lipid profiles and mesenchymal characteristics were NKG2A inhibitor presents a promising prospect in treating
consistent with samples obtained from patients diagnosed patients with BC expressing HLA-E. Although the study
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with high-grade BC. Inhibition of GD2 synthesis led to is not directly relevant to BCSCs, it is reasonable to infer that
the upregulation of E-cadherin and downregulation of BCSCs may exploit various immune checkpoint inhibition
vimentin, indicating a positive association between elevated pathways, leading to the lower response rates observed
GD2 levels and EMT, which facilitates tumor metastasis with mono-immunotherapy using immune checkpoint
and the transformation into a more malignant BC. This inhibitors in patients with BC. However, unlike in other
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process involved the reprogramming of the GD2 synthesis cancer types, direct evidence of immune evasion by BCSCs
pathway, directly influencing the malignancy of the tumor is currently lacking. Therefore, further investigation into
and enhancing the metastatic abilities of BCSCs. the crosstalk between BCSCs and immune evasion is
warranted to uncover new therapeutic avenues.
The metabolic pathways of BCSCs undergo specific
alterations compared to other cells. By exploring 3.8. Targeted therapy
differences in metabolite levels, researchers can investigate Given the significant role of BCSCs in tumor drug
the interplay between various metabolic pathways and resistance and relapse, a comprehensive treatment strategy
tumor progression, consequently identifying new targets is required to target BCSCs, thereby eliminating residual
for BC treatment. BCSCs and mitigating the risk of recurrence. While

3.7. Immune evasion standard chemotherapy has proven effective against
BCNSCs, its efficacy against BCSCs is generally limited.
Immune checkpoint inhibitors have revolutionized the Current targeted therapy mainly consists of molecular
therapy landscape for patients with BC; however, their inhibitors that target specific pathways, as well as drug
efficacy remains limited, with response rates ranging conjugates with antibodies designed to target specific
from 10 – 20%. The limitation stems from the interaction biomarkers.
between programmed death-ligand 1 (PD-L1) on tumor
cells and programmed cell death protein 1 (PD-1) on 3.8.1. Immunotoxin-monoclonal antibody complex
immune cells, which inhibit the effector function of treatment
immune cells, ultimately inducing the exhaustion of The abnormal glycosylation of integrin α3β1 on the
immune cells. A study has uncovered that the expression surface of BC cells could serve as a biomarker for BC. Our
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of PD-L1 may contribute to immune evasion in BCSCs. group have developed a specific antibody named BCMab1
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Moreover, recent research has identified CD44 not only as aimed at targeting this antigen. BCMab1 was further
a classical marker of BCSCs but also as a potential target for conjugated with ricin A chain (Ra), a cytotoxic agent. In
immunotherapy. Specifically, Liu et al. have revealed that an experimental setting where T24 cells were transplanted
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knockdown of CD44, along with the decreased expression into mice and continuously treated with BCMab1-Ra, the
of PD-L1, may promote the progression of BC by affecting mice exhibited a sustained survival rate of over 80% even
the immunosuppressed M2 macrophages. 102 after 100 days. In contrast, treatment with BCMab1 alone
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Activation of STAT3 could upregulate the expression of resulted in the demise of all mice within 80 days. These
the inhibitory receptor in both TSCs and macrophages, 103,104 findings underscore the effectiveness of BCMab1-Ra in
leading to suppression of T-cell proliferation through the targeting and eliminating tumor cells, thereby inhibiting
expansion of macrophages and regulatory T cells. 105,106 the growth of subcutaneous and in situ BC in mouse
Given the high expression of STAT3 observed in BCSCs, models.
as mentioned in the KMT1A-GATA3-STAT3 pathway, Subsequently, our group conducted a preliminary
STAT3 may play an important role in the immune evasion clinical study wherein a patient with multiple BCs was
of BCSCs, highlighting the importance of targeting the treated using intravesical infusion of BCMab1-Ra.
STAT3 pathway to eliminate BCSCs. On the other hand, Remarkably, after 26 weeks of treatment, the tumors
recent research has elucidated that NKG2A CD8 T cells disappeared, and no local or systemic side effects were
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exhibit robust activation ability independent of the T cell observed. The patient remained tumor-free during the
receptor in BC. These cells can directly eliminate tumor follow-up examinations conducted every 6 months for
cells with low expression of human leucocyte antigen 3 years. Despite these encouraging outcomes, there
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Volume 1 Issue 1 (2024) 39 doi: 10.36922/mi.2377