Increased regulatory B cells are involved in immune evasion in patients with gastric cancer

Murakami, Yuki; Saito, Hiroaki; Sasaki, Shota; Kono, Yusuke; Shishido, Yuji; Miyatani, Kozo; Matsunaga, Tomoyuki; Fukumoto, Yoshihiro; Ashida, Keigo; Sakabe, Tomohiko; Nakayama, Yuji; Fujiwara, Yoshiyuki

doi:10.1038/s41598-019-49581-4

Cited by 87 publications

(69 citation statements)

References 26 publications

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“…Survival analysis showed that five-year OS rates in the Breg Low group were significantly higher than those in the Breg High group. Multivariate analysis revealed that the percentage of Bregs in tumor tissue was an independent prognostic indicator of GC patient survival (50). This study indicates that Breg-related immunosuppression is closely correlated to tumor progression.…”

Section: Potential Of Bregs As Biomarkers and Prognostic Factors Formentioning

confidence: 59%

Phenotypes, Functions, and Clinical Relevance of Regulatory B Cells in Cancer

Shang

Zha²,

Sun

2020

Front. Immunol.

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In immune system, B cells are classically positive modulators that regulate inflammation and immune responses. Regulatory B cells (Bregs) are a subset of B cells which play crucial roles in various conditions, including infection, allergies, autoimmune diseases, transplantation, and tumors. Until now, unequivocal surface markers for Bregs still lack consensus, although numerous Breg subsets have been identified. Generally, Bregs exert their immunoregulatory functions mainly through cytokine secretion and intercellular contact. In the tumor microenvironment, Bregs suppress effector T cells, induce regulatory T cells and target other tumor-infiltrating immune cells, such as myeloidderived suppressor cells, natural killer cells and macrophages, to hamper anti-tumor immunity. Meanwhile, the cross-regulations between Bregs and tumor cells often result in tumor escape from immunosurveillance. In addition, accumulating evidence suggests that Bregs are closely associated with many clinicopathological factors of cancer patients and might be potential biomarkers for accessing patient survival. Thus, Bregs are potential therapeutic targets for future immunotherapy in cancer patients. In this review, we will discuss the phenotypes, functions, and clinical relevance of Bregs in cancer.

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Section: Potential Of Bregs As Biomarkers and Prognostic Factors Formentioning

confidence: 59%

Phenotypes, Functions, and Clinical Relevance of Regulatory B Cells in Cancer

Shang

Zha²,

Sun

2020

Front. Immunol.

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“…Tumor-infiltrating mononuclear cells were isolated from 15 GC patients who underwent gastrectomy as previously described [13]. In brief, fresh cancer tissues and non-cancerous gastric mucosa (at least 5 cm apart from the tumor in the resected specimen) were cut into small pieces with a size of approximately 1 mm, and digested with 0.002% DNase I, 0.08% collagenase IV, and 0.01% hyaluronidase (all from Worthington, Lakewood, NJ, USA) at 37°C for 60 min.…”

Section: Isolation Of Tumor-infiltrating Mononuclear Cellsmentioning

confidence: 99%

“…Immunohistochemistry was carried out using samples from 102 patients with stage I-III gastric adenocarcinoma as previously described [13]. Four μm-thick paraffin sections were dewaxed, deparaffinized in xylene, and rehydrated through a graded alcohol series.…”

Section: Immunohistochemistry Assaymentioning

confidence: 99%

Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients

Kono

Saito²,

Miyauchi

et al. 2020

BMC Cancer

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Background: Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells. Although recent studies indicate that PD-1 is also expressed on other immune cells besides T cells, its role remains unclear. This study aims to evaluate PD-1 expression on macrophages and examine its effect on anti-tumor immunity in gastric cancer (GC) patients. Methods: The frequency of PD-1 + macrophages obtained from GC tissue was determined by multicolor flow cytometry (n = 15). Double immunohistochemistry staining of PD-1 and CD68 was also performed to evaluate the correlations among the frequency of PD-1 + macrophages, clinicopathological characteristics, and prognosis in GC patients (n = 102). Results: The frequency of PD-1 + macrophages was significantly higher in GC tissue than in non-tumor gastric tissue. The phagocytotic activity of PD-1 + macrophages was severely impaired compared with that of PD-1 − macrophages. The 5-year disease-specific survival rates in patients with PD-1 + macrophage Low (the frequency of PD-1 + macrophages; < 0.85%) and those with PD-1 + macrophage High (the frequency of PD-1 + macrophages; ≥ 0.85%) were 85.9 and 65.8%, respectively (P = 0.008). Finally, multivariate analysis showed the frequency of PD-1 + macrophage to be an independent prognostic factor. Conclusions: The function of PD-1 + macrophage was severely impaired and increased frequency of PD-1 + macrophage worsened the prognosis of GC patients. PD-1-PD-L1 therapies may function through a direct effect on macrophages in GC.

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“…Tumor-infiltrating mononuclear cells were isolated form 15 GC patients who underwent gastrectomy as previously described [13]. In brief, fresh cancer tissues and non-cancerous gastric mucosa (at least 5 cm apart from the tumor in the resected specimen) were cut into small pieces with a size of approximately 1mm, and digested with 0.002% DNase I, 0.08% collagenase IV, and 0.01% hyaluronidase (all from Worthington, Lakewood, NJ, USA) at 37°C for 60 min.…”

Section: Isolation Of Tumor-infiltrating Mononuclear Cellsmentioning

confidence: 99%

“…Immunohistochemistry was carried out using samples from 102 patients with stage I-III gastric adenocarcinoma as previously described [13]. Four µm-thick paraffin sections were dewaxed, deparaffinized in xylene, and rehydrated through a graded alcohol series.…”

Section: Immunohistochemistry Assaymentioning

confidence: 99%

Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients.

Kono

Saito

Miyauchi

et al. 2020

Preprint

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Background: Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells. Although recent studies indicate that PD-1 is also expressed on other immune cells besides T cells, its role remains unclear. This study aims to evaluate PD-1 expression on macrophages and examine its effect on anti-tumor immunity in gastric cancer (GC) patients. Methods : The frequency of PD-1 + macrophages obtained from GC tissue was determined by multicolor flow cytometry (n = 15). Double immunohistochemistry staining of PD-1 and CD68 was also performed to evaluate the correlations among the frequency of PD-1 + macrophages, clinicopathological characteristicus, and prognosis in GC patients (n = 102). Results: The frequency of PD-1 + macrophages was significantly higher in GC tissue than in non-tumor gastric tissue. The phagocytotic activity of PD-1 + macrophages was severely impaired compared with that of PD-1 - macrophages. The 5-year disease specific survival rates in patients with PD-1 + macrophage Low (the frequency of PD-1 + macrophages; < 0.85%) and those with PD-1 + macrophage High (the frequency of PD-1 + macrophages; ≥ 0.85%) were 85.9% and 65.8%, respectively ( P = 0.008). Finally, multivariate analysis showed the frequency of PD-1 + macrophage to be an independent prognostic factor. Conclusions: The function of PD-1 + macrophage was severely impaired and increased frequency of PD-1 + macrophage worsened the prognosis of GC patients. PD-1–PD-L1 therapies may function through a direct effect on macrophages in GC.

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Increased regulatory B cells are involved in immune evasion in patients with gastric cancer

Cited by 87 publications

References 26 publications

Phenotypes, Functions, and Clinical Relevance of Regulatory B Cells in Cancer

Phenotypes, Functions, and Clinical Relevance of Regulatory B Cells in Cancer

Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients

Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients.

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