Metastatic tumour cells favour the generation of a tolerogenic milieu in tumour draining lymph node in patients with early cervical cancer

Battaglia, Alessandra; Buzzonetti, Alexia; Baranello, Cinzia; Ferrandina, Gabriella; Martinelli, Elisa; Fanfani, Francesco; Scambia, Giovanni; Fattorossi, Andrea

doi:10.1007/s00262-008-0646-7

Cited by 69 publications

(68 citation statements)

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“…2B). Our data on tonsil samples are concordant with the previous data from Dzionek et al [14] [16]. A tolerogenic cytokine milieu might therefore increase the amount of regulatory phenotype Nrp-1 1 T cells and this could be an explanation for our heterogeneous and apparently diverging results.…”

Section: Nrp-1-expressing T Cells In Secondary Lymphoid Organssupporting

confidence: 92%

Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

et al. 2009

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Treg are immune cells that play a critical role in the regulation of the immune response. Although the transcription factor Foxp3 is widely accepted as the standard marker of Treg, specific surface markers are needed to better characterize these cells and decipher their mechanisms of action. Neuropilin-1 (Nrp-1), a membrane protein primarily involved in the nervous system, was identified as a specific marker of murine Treg, but its expression has not been rigorously investigated in human Treg. Here we show that in contrast to murine Treg and regardless of their origins (blood, thymus, spleen, lymph node or tonsil), human Foxp3 1 Treg do not specifically express Nrp-1. However, a population of Foxp3 À Nrp-1 1 T cells can be detected in human secondary lymphoid organs, and Nrp-1 expression is induced on peripheral blood T lymphocytes upon in vitro activation. We conclude that Nrp-1 cannot be used as a specific marker of human Treg, but might represent a novel activation marker of human T cells both in vitro and in vivo.

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Section: Nrp-1-expressing T Cells In Secondary Lymphoid Organssupporting

confidence: 92%

Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

et al. 2009

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“…The balance between infiltrating CD8+ T cells and Tregs was found to be an independent prognostic factor for patient survival [49]. Metastatic tumor cells in tumor draning lymph nodes were found to correlate with increased numbers of Treg in the respective lymph node [127].…”

Section: T Regulatory Cells In Cervical Cancer Patientsmentioning

confidence: 99%

“…In humans, cyclophosphamide used as a single agent was shown to inhibit the Treg compartment, while the effector compartment was not negatively influenced [161,162]. In cervical cancer patients Treg numbers were decreased after preoperative low-dose chemoradiation therapy [127,163]. Combinational therapy has not been studied in cervical cancer patients, but may prove to be an effective approach to enhance anti-tumor vaccination strategies.…”

Section: Depletion Of Tregs Based On Cytotoxic Chemotherapymentioning

confidence: 99%

Immunosuppressive Tumor Microenvironment in Cervical Cancer Patients

Piersma

2011

Cancer Microenvironment

105

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Cervical cancer is caused by Human papillomavirus (HPV) in virtually all cases. These HPV-induced cancers express the viral oncogenes E6 and E7 and are therefore potentially recognized by the immune system. Despite the abundant presence of these foreign antigens, the immune system is unable to cope with the tumor. Due to the constant immunological pressure, cervical cancers can evolve different immune evasion strategies, which will be described in the current review. Several approaches for immunotherapy of cervical cancer are currently under development, which aim at inducing strong HPV-specific immunity. Besides the reinforcement of potent anti-tumor immune responses, immunotherapy could also enhance HPV-specific T regulatory cells. Supplementary strategies that neutralize an immunosuppressive milieu may have great potential. These strategies are discussed as well.

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“…In such situation, primary tumor risk factors can be used for guiding adjuvant treatment. Moreover, leaving unaltered the lymphatic system might have another positive effect, thanks to the potential immunological surveillance of metastasis‐free LNs proximal to the tumor 30, 31. On the other hand although the clinical role of micrometastases is still far from being clarified, the risk of missing useful information avoiding ultrastaging of SLN biopsy cannot be denied.…”

Section: Discussionmentioning

confidence: 99%

Beyond sentinel node algorithm. Toward a more tailored surgery for cervical cancer patients

et al. 2016

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Nowadays cervical cancer is frequently diagnosed at early stage. For these patients lymph node metastasis (LNM) is considered the most important prognostic factor. During the last decade many efforts have been made to reduce rate of complications associated with lymphadenectomy (LND). A great interest has arisen in sentinel lymph node (SLN) biopsy as a technique able to decrease number of LND performed and, at the same time, to assess lymph nodal status. High diagnostic performances have been reached thanks to SLN surgical algorithm. However, despite the efforts, about 25% of these patients undergo at least unilateral LND to meet NCCN recommendations. Data of women with International Federation of Gynecology and Obstetrics stage IA1‐IB1/IIA1 cervical carcinoma were retrospectively collected by six Italian institutions. All patients underwent complete preoperative staging workup and were primarily treated by radical hysterectomy and pelvic bilateral LND. A total of 368 patients with early‐stage cervical cancer were identified. Among them 333 (90.5%) showed no suspicious enlarged nodes at the preoperative magnetic resonance imaging (MRI). In this subset, tumor diameter ≥20 mm was the only independent predictor of LN status (P = 0.003). None of the 106 patients with negative MRI nodal assessment, with squamous and adenosquamous histotype and a tumor diameter less than 2 cm had LNM. Based on these results we propose a new modified SLN surgical algorithm that could safely reduce LND performed in patients with very low‐risk early‐stage cervical cancer.

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Metastatic tumour cells favour the generation of a tolerogenic milieu in tumour draining lymph node in patients with early cervical cancer

Cited by 69 publications

References 50 publications

Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

Immunosuppressive Tumor Microenvironment in Cervical Cancer Patients

Beyond sentinel node algorithm. Toward a more tailored surgery for cervical cancer patients

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Metastatic tumour cells favour the generation of a tolerogenic milieu in tumour draining lymph node in patients with early cervical cancer

Cited by 69 publications

References 50 publications

Neuropilin‐1 is not a marker of human Foxp3+ Treg

Neuropilin‐1 is not a marker of human Foxp3+ Treg

Immunosuppressive Tumor Microenvironment in Cervical Cancer Patients

Beyond sentinel node algorithm. Toward a more tailored surgery for cervical cancer patients

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Product

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Neuropilin‐1 is not a marker of human Foxp3⁺ Treg

Neuropilin‐1 is not a marker of human Foxp3⁺ Treg