CD20+ B Cells: The Other Tumor-Infiltrating Lymphocytes

Nelson, Brad H.

doi:10.4049/jimmunol.1001323

Cited by 361 publications

(303 citation statements)

References 91 publications

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“…High B-cell density is said to be associated with improved outcome in gastric, breast and colorectal cancer (9)(10)(11), as well as squamous cell carcinoma of the tongue (12), melanoma and hepatocellular carcinoma (5,13). The same correlation has been shown for pancreatic adenocarcinomas, though here the impact was only measurable if cells were arranged in the pattern of TLSs (4,14).…”

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confidence: 61%

High Density of Tumor-infiltrating B-Lymphocytes and Plasma Cells Signifies Prolonged Overall Survival in Adenocarcinoma of the Esophagogastric Junction

Knief

Reddemann

Petrova

et al. 2016

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Abstract. Background: Tumor-infiltrating lymphocytes (TILs) have been shown to be of prognostic significance in a variety of tumors. Not only T-cell, but also B-cell In recent years, studies concerning the microenvironment of tumors, especially tumor-infiltrating lymphocytes (TILs), have been abundant. This microenvironment has been shown to influence overall survival (OS), as well as relapse times, and probability of tumor recurrence (1, 2). However, most studies have focused on the relationship between T-cell infiltration and patients' outcome, while the role of tumor infiltrating B-lymphocytes (TIL-Bs), as well as plasma cells in this setting, is still poorly understood and less commonly investigated.Not only the presence, but also the distribution pattern has been described as being crucial to prognosis: In carcinomas, immune cells are predominantly found in the stroma (3) and the formation of dense, follicle-like lymphocyte infiltrates (so-called tertiary lymphatic structures (TLSs), which arise in non-lymphoid tissues, often in the context of chronic inflammation) has been reported to have the strongest impact on prognosis and survival (2, 4, 5).T-lymphocytes (especially cytotoxic T-cells), as well as Blymphocytes, increase and establish the activation of antitumoral immunity (as an adaptive mechanism), leading to increased cell death in tumors and resulting in improved prognosis in patients with high levels of TILs (2, 6). Tumorassociated plasma cells have been described to have a significant impact on prognosis through modulation of the humoral immune response (7).Up to date, most reports in the literature state a positive effect of TILs in respect to OS, relapse-free survival and association with favorable prognostic factors, as well as lower T-stage (8). High B-cell density is said to be associated with improved outcome in gastric, breast and colorectal cancer (9-11), as well as squamous cell carcinoma of the tongue (12), melanoma and hepatocellular carcinoma (5, 13). The same correlation has been shown for pancreatic adenocarcinomas, though here the impact was only measurable if cells were arranged in the pattern of TLSs (4,14). High proportions of TILs have also been shown to be predictive of response to neoadjuvant therapy in breast cancer patients (15). 5339

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confidence: 61%

High Density of Tumor-infiltrating B-Lymphocytes and Plasma Cells Signifies Prolonged Overall Survival in Adenocarcinoma of the Esophagogastric Junction

Knief

Reddemann

Petrova

et al. 2016

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“…As this involves a major surgery in the recipient mice, it could in turn create a local infl ammatory environment that promotes a higher-than-normal infi ltration of B cells into the tumor site, and hence the data obtained from these models should be interpreted with caution. Additionally, there are confl icting reports on the role of TIL-Bs in other tumor types, demonstrating the need for further study ( 2 ). Nevertheless, fi ndings from the three studies provide compelling evidence for the involvement of tumor-infi ltrating B cells in the initiation and progression of PDAC.…”

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confidence: 86%

“…In general, cytotoxic CD8 + T cells, Th1-type CD4 + T cells, and natural killer (NK) cells exhibit antitumor activity, whereas regulatory T cells, myeloid-derived suppressor cells (MDSC), and tumorassociated macrophages (TAM) suppress antitumor immune responses and promote tumor progression and metastasis ( 2 ). The role of B cells in neoplasia has also been evaluated in genetically modifi ed mouse models.…”

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confidence: 99%

B Cells Promote Pancreatic Tumorigenesis

et al. 2016

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Summary: Three recent studies, approaching the question from different angles and using different and/or overlapping models, provide compelling evidence for the involvement of tumor-infi ltrating B cells in the initiation and progression of pancreatic ductal adenocarcinoma. These studies highlight the need for a better understanding of pancreatic tumor-immune system interactions and the immunologic mechanisms that promote or inhibit tumorigenesis, paving the way for better treatment strategies. Cancer Discov; 6(3); 230-2. ©2016 AACR.See related article by p. 247 (8).See related article by Lee et al., p. 256 (9).See related article by Gunderson et al., p. 270 (10).Treatment of pancreatic cancer has proven very diffi cult because of both the low/nonimmunogenic nature of the tumor and the late stages at diagnosis. This is refl ected in the abysmal 5-year survival rate of ∼ 7% and the harsh standard-of-care (SOC) for patients. The most common treatment, aside from palliative care or surgery in eligible patients, is gemcitabine, which is a general DNA-damaging agent. However, those patients healthy enough to handle strong treatment side effects are given a cocktail of four drugs called FOLFIRINOX in the hope of stalling tumor development. Other FDA-approved drug combinations may be tried as the fi rst-line treatment, but all have signifi cant side effects affecting patient quality of life without much measurable benefi t. Although no immunotherapies are currently approved for treating pancreatic cancers, there are 16 clinical trials of various immunotherapies for this disease (clinicaltrials. gov). These trials fall into two categories: combination therapies and vaccines. Most of the combination therapies involve adding an immunotherapy-like checkpoint blockade, vaccine, or cytokines to the SOC, aiming to fi rst make pancreatic ductal adenocarcinoma (PDAC) immunogenic and then promote antitumor immune responses ( 1 ).Studies in both human and animal models have now demonstrated that the immune system plays a critical role in modulating the outcome of tumor development. In general, cytotoxic CD8 + T cells, Th1-type CD4 + T cells, and natural killer (NK) cells exhibit antitumor activity, whereas regulatory T cells, myeloid-derived suppressor cells (MDSC), and tumorassociated macrophages (TAM) suppress antitumor immune responses and promote tumor progression and metastasis ( 2 ). Increasingly, B cells are also found to play a signifi cant role in modulating the growth and progression of solid tumors ( 2, 3 ). Tumor-infi ltrating lymphocytic B cells (TIL-B) are a major component of TILs in breast and advanced ovarian cancers, and their presence correlates with improved survival. However, in multiple mouse models, tumor development is enhanced when B cells are present. Growth of EL4 thymoma, MC38 colon cancer, and EMT6 breast cancer is signifi cantly inhibited in B cell-defi cient mice. The absence of B cells is associated with increased infi ltration of Th1 cells, CD8 + T cells, and NK cells in the tumor. Conversely, ad...

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“…Lymphocytic infiltrates within solid tumors are well-recognized positive predictors of survival (11). Notably, B cells are a significant component of these infiltrates.…”

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confidence: 99%

Multiplex B Cell Characterization in Blood, Lymph Nodes, and Tumors from Patients with Malignancies

Zirakzadeh

Marits

Sherif

et al. 2013

The Journal of Immunology

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B lymphocytes contribute to immune surveillance, by tumor-specific Abs and Ag presentation to T lymphocytes, but are insufficiently studied in humans. In this article, we report a flow cytometric investigation of B lymphocyte subpopulations in blood, lymph nodes (LNs), and malignant tissues from 20 patients operated on because of advanced solid tumors. The CD19+ compartment in peripheral blood was essentially unaltered in patients, as compared with healthy control subjects. In metastatic LNs, signs of B lymphocyte activation were observed, as evidenced by increased proportions of plasmablasts and CD86-expressing cells. In tumor-infiltrating B lymphocytes (TIL-B), both switched memory cells and plasmablasts were expanded, as compared with nonmalignant epithelium. Moreover, pronounced skewing of Igλ/Igκ ratio was evident among TIL-Bs. By spectratype analysis on IgH, we confirmed a monoclonal expansion of the Vh7 family in TIL-B, also present in a tumor-associated LN. Sequencing the clonally expanded Vh7 revealed signs of somatic hypermutation. In conclusion, B lymphocytes in cancer patients exhibit signs of activation in tumor-associated tissues, likely induced by recognition of tumor Ags. Increased numbers of switched memory cells and plasmablasts in combination with clonal expansion and signs of somatic hypermutation suggest a CD4+ T lymphocyte–dependent antitumoral response, which may be exploited for immunotherapy.

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CD20+ B Cells: The Other Tumor-Infiltrating Lymphocytes

Cited by 361 publications

References 91 publications

High Density of Tumor-infiltrating B-Lymphocytes and Plasma Cells Signifies Prolonged Overall Survival in Adenocarcinoma of the Esophagogastric Junction

High Density of Tumor-infiltrating B-Lymphocytes and Plasma Cells Signifies Prolonged Overall Survival in Adenocarcinoma of the Esophagogastric Junction

B Cells Promote Pancreatic Tumorigenesis

Multiplex B Cell Characterization in Blood, Lymph Nodes, and Tumors from Patients with Malignancies

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