PD-L1 mediated the differentiation of tumor-infiltrating CD19⁺B lymphocytes and T cells in Invasive breast cancer

Abstract

Accumulating evidence suggests that B cells play important roles in inhibiting the immune response in autoimmune disorders and human tumors as well as murine tumor models. In an effort to explore the role of B cells in human breast cancer etiology, we examined the presence of CD19 C B lymphocytes in 134 cases of invasive breast carcinoma (IBCa) and 31 breast fibroadenoma, and assessed its relationship with PD-L1 (programmed death-ligand 1) expression in breast cancer. We found that the density of CD19 C B lymphocytes was higher in IBCa compared with fibroadenoma, and significantly associated with increasing tumor grade, negative estrogen status. Similar findings were observed for the expression of IL-10 in IBCa. Meanwhile, CD19C B lymphocytes were shown to be highly coincident with PD-L1 and IL-10 in IBCa. We further demonstrated that CD19 C B cells can differentiate into CD19 Foxp3C T cells by CD19 C B cells was further shown to be mediated by PD-L1. Together, these results are suggestive of a role for CD19 C B lymphocytes in immune suppression and tumor evasion via PD-L1 in breast cancer.

Tumor infiltrating CD19+ B lymphocytes predict prognostic and therapeutic benefits in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

“…A recent randomized, phase 3 trial involving previously untreated patients with advanced renal cell carcinoma showed that the overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib. 32 Even so, the response rates to anti-PD-1 antibody were only 27%, which is far from satisfied, in patients with renal cancer. 33 Predictive biomarkers exist to guide selection for immune checkpoint inhibitors are still not routinely used in the clinic yet.…”

B‐cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: Influence of ruxolitinib, interferon‐α2, or combination treatment

“…Contrarily, a recent study has shown that the JAK2 ‐V617F mutation increases the expression of PD‐L1 on various cell types in patients with MPNs, but not in B cells . Upregulated expression of PD‐L1 on Bregs has also been observed in patients with invasive breast cancer, where the interaction of B‐cell PD‐L1 with PD‐1 on T cells promoted a Treg phenotype, and tumor‐infiltrating B cells have been suggested to play an important role in promoting tumor progression . Therefore, the increased proportion of PD‐L1 + B cells in MPNs presumably reflects an increased immunoregulatory potential of the B‐cell pool.…”

“…In addition, B cells express programmed cell death protein ligand 1 (PD‐L1), the binding of which to programmed death‐1 receptor (PD‐1) on T cells represents a major checkpoint that regulates immune response and allows the growth of cancers . Specifically, PD‐L1 is upregulated on peripheral Bregs from patients with invasive breast cancer, and interaction of B‐cell PD‐L1 with PD‐1 on T cells promotes a regulatory T‐cell (Treg) phenotype in this disease . Activated B cells also express PD‐1, and an immunoregulatory role of IL‐10‐producing PD‐1 hi B cells has been suggested in hepatocellular carcinoma .…”

“…with PD-1 on T cells promotes a regulatory T-cell (Treg) phenotype in this disease. 15,16 Activated B cells also express PD-1, 17 and an immunoregulatory role of IL-10-producing PD-1 hi B cells has been suggested in hepatocellular carcinoma. 18 It is therefore conceivable that the B-cell phenotype pattern in patients with MPNs influences the development of immune deregulation and associated complications, including second cancers.…”

A new perspective: Exploring future therapeutic strategies for cancer by understanding the dual role of B lymphocytes in tumor immunity

“…However, Guan et al 36 showed that more CD19 + B lymphocytes are present in invasive breast carcinoma (IBCa) than fibroadenoma and are significantly associated with a negative estrogen status and increasing tumor grade. At the same time, CD19 + B cells were found to be highly coincident with PD-L1 and IL-10 in IBCa.…”