A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis

Miyatani, Kozo; Saito, Hiroaki; Murakami, Yuki; Watanabe, Junya; Kuroda, Hirohiko; Matsunaga, Tomoyuki; Osaki, Tomohiro; Nakayama, Yuji; Umekita, Yoshihisa; Ikeguchi, Masahide

doi:10.1007/s00428-016-1914-0

Cited by 25 publications

(37 citation statements)

References 50 publications

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“…Neoplastic conditions associated with IgG4 + PCs have been reported in sclerosing mucoepidermoid carcinoma of the salivary gland [14,15], non-small-cell lung cancers [16], extrahepatic cholangiocarcinoma [17], gastric cancer [18] and Warthin tumor [19]. The exact prevalence and nature of this phenomenon are still uncertain.…”

Section: Discussionmentioning

confidence: 99%

Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto’s thyroiditis

et al. 2018

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Abstract. Hashimoto's thyroiditis with heavy lymphoplasmacytic infiltration is a common comorbidity of immunoglobulin G4 (IgG4)-related thyroiditis and Warthin-like papillary thyroid carcinoma (WL-PTC). We hypothesized that WL-PTC may have a strong association with IgG4-related thyroiditis. To validate this hypothesis, we clinically and immunohistochemically studied 17 WL-PTC cases. Fourteen patients (82.4%) had anti-thyroglobulin antibody and were confirmed to have Hashimoto's thyroiditis through microscopic analysis. Among them, five (29.4%) had disease consistent with IgG4-related thyroiditis but did not exhibit a "storiform" pattern or obliterative phlebitis. IgG4-related diseases were not found in other organs. No cases with serum IgG4 level of >135 mg/dL were noted. A total of 94.1% of WL-PTC cases had IgG4-positive plasma cells ( + PCs) in the stroma, and cases with rich IgG4 + PCs were more frequently associated with Hashimoto's thyroiditis than those with poor IgG4 + PCs. In this study, all three cases without Hashimoto's thyroiditis had poor IgG4 + PCs, and one of them did not exhibit IgG4 + PCs in the stroma of WL-PTC and Hashimoto's thyroiditis. Nodal metastatic lesions were seen in eight cases, all of which were not WL-PTC. As such, we should consider that the Hashimoto's disease with rich IgG4 + PCs seen in our cases is representative of non-IgG4-related disease and not IgG4-related disease involving multiple organs. This study is the first to demonstrate the presence of IgG4 + PCs in the stroma of WL-PTC. We concluded that the appearance of IgG4 + PCs in the stroma of WL-PTC may be related to Hashimoto's thyroiditis with rich IgG4 + PC.

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Section: Discussionmentioning

confidence: 99%

Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto’s thyroiditis

et al. 2018

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“…IgG4 þ PC are associated with fibroinflammatory disease and may play an immunosuppressive role in cancer (61). Accordingly, IgG4 þ cells were found to have a negative prognostic effect in gastric cancer (62) and PDAC (63), but were not prognostic in NSCLC (16). Bosisio and colleagues found that IgA þ CD138 þ TIL were associated with poor prognosis in melanoma (58), which was opposite to the results reported when CD138 was used as a single marker in this setting (43).…”

Section: Plasma Cellsmentioning

confidence: 98%

Prognostic Significance of Tumor-Infiltrating B Cells and Plasma Cells in Human Cancer

Wouters¹,

Nelson

2018

Clinical Cancer Research

352

262

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There is abundant evidence that tumor-infiltrating CD8 T cells contribute positively to antitumor immunity; however, the role of tumor-infiltrating B cells (TIL-B) and plasma cells (PC) remains controversial, leading to differing opinions about whether immunotherapies should be designed to enhance or inhibit these cells. Through a comprehensive PubMed search, we reviewed publications with cohorts of 50 or more cases in which the prognostic value of TIL-B/PC was assessed by immunohistochemistry and/or gene-expression analysis. Sixty-nine studies representing 19 cancers met our review criteria. The large majority of studies assessed TIL-B by immunohistochemical detection of CD20. Of these, 50.0% reported a positive prognostic effect for CD20 TIL-B, whereas the remainder found a neutral (40.7%) or negative (9.3%) effect. These differences in prognostic effect were not attributable to cancer type, other clinicopathologic factors, or differing technical approaches. The prognostic significance of TIL-B/PC was generally concordant with that of CD3 and/or CD8 T cells, and the prognostic effect of T cells was generally stronger when TIL-B and/or PC were also present. Additionally, 21 studies inferred the presence of TIL-B/PC from gene-expression data, and a large majority reported a positive prognostic effect. Although more studies are required involving additional cancer types and independent patient cohorts, the weight of evidence supports a positive role for TIL-B and PC in antitumor immunity, suggesting that enhancement of these responses should be considered in the design of cancer immunotherapies.

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“…Immunofluorescence staining for PD-1 and CD68 was performed as previously described [15]. Four μm thick paraffinembedded sections were incubated with primary antibodies, which were the same antibodies used in immunohistochemistry, overnight at 4°C.…”

Section: Immunofluorescence Stainingmentioning

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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A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis

Cited by 25 publications

References 50 publications

Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto’s thyroiditis

Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto’s thyroiditis

Prognostic Significance of Tumor-Infiltrating B Cells and Plasma Cells in Human Cancer

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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