Detection of Immune Responses Against Urinary Bladder Cancer in Sentinel Lymph Nodes

Marits, Per; Karlsson, Matilda; Sherif, Amir; Garske, Ulrike; Thörn, Magnus; Winqvist, Ola

doi:10.1016/j.eururo.2005.09.010

Cited by 40 publications

(44 citation statements)

References 21 publications

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“…Yet, it remains to be demonstrated whether they play this role in humans with solid tumors. We have previously described that a tumor-specific Th1 response is present in sentinel LNs in colon and bladder cancer (42,43), and that sentinel node-acquired CD4 + T cells are promising for use in adoptive immunotherapies (1). In this study, we emulated sentinel node-resident total APCs for ex vivo T cell activation and expansion.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Responses were of varying magnitude and tended to be weaker or absent in patients with metastatic sentinel nodes (Table 2 and Figure 1B). We have recently described proliferative responses against the autologous tumour in sentinel nodes draining urinary bladder cancers (Marits et al, 2006), further supporting the immunological value of the sentinel node detection method. In the three Duke's B patients no 6 -8 dose-dependent proliferation was also detected in nonsentinel lymph nodes.…”

Section: Discussionmentioning

confidence: 55%

Sentinel node lymphocytes: tumour reactive lymphocytes identified intraoperatively for the use in immunotherapy of colon cancer

et al. 2006

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The sentinel node is the first lymph node to receive lymphatic drainage from a tumour and is usually the first site of metastases. Today, the sentinel node is used for tumour staging. Here, we focus on its immunological role and investigate lymphocytic function in sentinel nodes, identified intraoperatively by peritumoural dye injection, from 15 patients with colon cancer. Tumour infiltrating lymphocytes, sentinel and nonsentinel lymph node cells and peripheral blood leukocytes were studied by flow cytometry, proliferation assays and interferon-g secretion after activation with autologous tumour homogenate. Whereas tumour-infiltrating lymphocytes were nonresponsive in the proliferation assays, lymphocytes from sentinel nodes proliferated dose dependently and secreted interferon-g upon stimulation with tumour homogenate. The responses were of varying magnitude and tended to be weaker in metastatic sentinel nodes. Sentinel node lymphocytes represents an enriched source of tumour reactive lymphocytes, and may be useful in future trials of adoptive immunotherapy.

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“…Some surgeons, notably in the Nordic countries, have utilized a more limited template involving the obturator fossae alone, below the common iliac bifurcations [19,44]. Concerns have been raised that such Metastasis in a lymph node >5 cm limited templates may miss nodal metastases that would be removed with a larger template, however [44,45].…”

Section: Extent Of Lymphadenectomy In Bladder Cancermentioning

confidence: 98%

“…This is because the lymphatic drainage of the bladder is highly variable [19]. Several studies have demonstrated that even for unilateral bladder cancers, metastases may occur on the contralateral side in almost half of cases, and may be the only site of nodal metastases in 15% [20,21].…”

Section: Nodal Nomenclature and Tnm Stagingmentioning

confidence: 99%

Lymph node assessment and lymphadenectomy in bladder cancer

Sharir

Fleshner

2009

Journal of Surgical Oncology

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Lymph node status is a key prognostic indicator in patients with bladder cancer, so lymphadenectomy is important for accurate staging. Moreover, lymphadenectomy is curative for some patients with nodal metastases. Although there is evidence that the quality of regional node dissection is associated with oncologic outcome, controversy exists because other factors may also explain this observation. Consequently, there is no consensus regarding the optimal extent of lymphadenectomy and number of nodes that should be assessed.

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Detection of Immune Responses Against Urinary Bladder Cancer in Sentinel Lymph Nodes

Cited by 40 publications

References 21 publications

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

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

Sentinel node lymphocytes: tumour reactive lymphocytes identified intraoperatively for the use in immunotherapy of colon cancer

Lymph node assessment and lymphadenectomy in bladder cancer

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