A comparative study of the cellular immune response in patients with stage IB cervical squamous cell carcinoma. Low numbers of several immune cell subtypes are strongly associated with relapse of disease within 5 years

Nedergaard, Bettina; Ladekarl, Morten; Nyengaard, Jens Randel; Nielsen, Karsten

doi:10.1016/j.ygyno.2007.08.089

Cited by 91 publications

(63 citation statements)

References 19 publications

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“…Importantly, we identified and validated the presence of MIL-Bs and their penetration through the tumor capsule as independent favorable prognostic factors for patient survival and tumor recurrence. These findings corresponded with several previous reports that infiltrating B cells were prevalent in human cancers, recognizing a wide variety of tumor antigens, associating closely with T cells and other immune cells, and correlating with favorable outcomes (31,32). However, there were conflicting data suggesting that B cells had a negative effect on protective antitumor responses and might even facilitate tumor progression (33,34 including MHC I, MHC II, CD40, CD80, and CD86, so that MIL-Bs were capable of recognizing and presenting tumorassociated antigens.…”

Section: Discussionsupporting

confidence: 91%

Margin-Infiltrating CD20+ B Cells Display an Atypical Memory Phenotype and Correlate with Favorable Prognosis in Hepatocellular Carcinoma

Shi

Gao

Wang

et al. 2013

Clinical Cancer Research

168

155

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Purpose: The role of infiltrating B cells in hepatocellular carcinoma has been overlooked for many years. This study is aimed to delineate the distribution, prognostic value, and functional status of B cells in human hepatocellular carcinoma.Experimental design: Immunohistochemistry was used to investigate the distribution and clinical significance of infiltrating CD20þ B cells in a series of 120 patients with hepatocellular carcinoma. The results were further tested in an independent series of 200 patients with hepatocellular carcinoma. The functional status of CD20 þ B cells was determined by flow cytometry, immunofluorescence, and in vitro coculture assay.Results: Infiltrating CD20 þ B cells were predominantly concentrated in the tumor invasive margin, compared with the peri-and intratumor areas. High density of margin-infiltrating B lymphocytes (MIL-B) positively correlated with small tumor size, absence of vascular invasion, and increased density of CD8 þ T cells (P < 0.05). Survival analyses revealed that increased number of MIL-Bs and their penetration through the tumor capsule were significantly associated with improved overall and recurrence-free survival, and were identified as independent prognosticators for patients with hepatocellular carcinoma (P < 0.05). Importantly, the results were further validated in another independent hepatocellular carcinoma cohort. Moreover, we found that MIL-Bs featured an atypical memory phenotype (IgDexpressed surface markers characteristic of antigen-presenting cells, possessed tumor-killing potential by producing IFN-g, interleukin 12p40 (IL-12p40), granzyme B, and TRAIL, and acted in cooperation with CD8 þ T cells. Conclusions:The profile of CD20 þ B cells in situ is a new predictor of prognosis for patients with hepatocellular carcinoma and provides a novel target for an optimal immunotherapy against this fatal malignancy.

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Section: Discussionsupporting

confidence: 91%

Margin-Infiltrating CD20+ B Cells Display an Atypical Memory Phenotype and Correlate with Favorable Prognosis in Hepatocellular Carcinoma

Shi

Gao

Wang

et al. 2013

Clinical Cancer Research

168

155

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“…TIL-Bs are strongly correlated with survival in ovarian cancer (59 (63,64). In cervical cancer, CD20 + , CD4 + , and CD8 + TILs are associated with a lower relapse rate (65). Finally, TIL-B are prominent in germ cell tumors, where they show evidence of Ag-driven clonal expansion and affinity maturation (66).…”

Section: B Cells In Cancermentioning

confidence: 99%

CD20+ B Cells: The Other Tumor-Infiltrating Lymphocytes

Nelson

2010

The Journal of Immunology

346

278

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Tumor-infiltrating CD8+ T cells are strongly associated with patient survival in a wide variety of human cancers. Less is known about tumor-infiltrating CD20+ B cells, which often colocalize with T cells, sometimes forming organized lymphoid structures. In autoimmunity and organ transplantation, T cells and B cells collaborate to generate potent, unrelenting immune responses that can result in extensive tissue damage and organ rejection. In these settings, B cells enhance T cell responses by producing Abs, stimulatory cytokines, and chemokines, serving as local APCs, and organizing the formation of tertiary lymphoid structures that sustain long-term immunity. Thus, B cells are an important component of immunological circuits associated with persistent, rampant tissue destruction. Engagement of tumor-reactive B cells may be an important condition for generating potent, long-term T cell responses against cancer.

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“…Tumor-infiltrating B cells are also correlated with favorable outcomes in breast, cervical, and non-small cell lung cancer (9)(10)(11). In breast cancer and germ cell tumors, tumor-infiltrating B cells have been shown to consist of activated, antigen-experienced, oligoclonal subpopulations (12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

CD20+ Tumor-Infiltrating Lymphocytes Have an Atypical CD27− Memory Phenotype and Together with CD8+ T Cells Promote Favorable Prognosis in Ovarian Cancer

Nielsen

Sahota

Milne

et al. 2012

Clinical Cancer Research

449

360

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Purpose: Tumor-infiltrating lymphocytes (TIL), in particular CD8þ T cells and CD20 þ B cells, are strongly associated with survival in ovarian cancer and other carcinomas. Although CD8 þ TIL can mediate direct cytolytic activity against tumors, the role of CD20 þ TIL is poorly understood. Here, we investigate the possible contributions of CD20 þ TIL to humoral and cellular tumor immunity.Experimental Design: Tumor and serum specimens were obtained from patients with high-grade serous ovarian cancer. CD8þ and CD20 þ TIL were analyzed by immunohistochemistry and flow cytometry.Immunoglobulin molecules were evaluated by DNA sequencing. Serum autoantibody responses to the tumor antigens p53 and NY-ESO-1 were measured by ELISA.Results: The vast majority of CD20 þ TIL were antigen experienced, as evidenced by class-switching, somatic hypermutation, and oligoclonality, yet they failed to express the canonical memory marker CD27. CD20 þ TIL showed no correlation with serum autoantibodies to p53 or NY-ESO-1. Instead, they colocalized with activated CD8 þ TIL and expressed markers of antigen presentation, including MHC class I, MHC class II, CD40, CD80, and CD86. The presence of both CD20 þ and CD8 þ TIL correlated with increased patient survival compared with CD8 þ TIL alone. Conclusions:In high-grade serous ovarian tumors, CD20 þ TIL have an antigen-experienced but atypical CD27 À memory B-cell phenotype. They are uncoupled from serum autoantibodies, express markers of antigen-presenting cells, and colocalize with CD8 þ T cells. We propose that the association between CD20 þ TIL and patient survival may reflect a supportive role in cytolytic immune responses.

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A comparative study of the cellular immune response in patients with stage IB cervical squamous cell carcinoma. Low numbers of several immune cell subtypes are strongly associated with relapse of disease within 5 years

Cited by 91 publications

References 19 publications

Margin-Infiltrating CD20+ B Cells Display an Atypical Memory Phenotype and Correlate with Favorable Prognosis in Hepatocellular Carcinoma

Margin-Infiltrating CD20+ B Cells Display an Atypical Memory Phenotype and Correlate with Favorable Prognosis in Hepatocellular Carcinoma

CD20+ B Cells: The Other Tumor-Infiltrating Lymphocytes

CD20+ Tumor-Infiltrating Lymphocytes Have an Atypical CD27− Memory Phenotype and Together with CD8+ T Cells Promote Favorable Prognosis in Ovarian Cancer

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