Metastatic tumour cells favour the generation of a tolerogenic milieu in tumour draining lymph node in patients with early cervical cancer
| Autor: | Giovanni Scambia, Gabriella Ferrandina, Enrica Martinelli, Cinzia Baranello, Francesco Fanfani, Andrea Fattorossi, Alexia Buzzonetti, Alessandra Battaglia |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Vascular Endothelial Growth Factor A Cancer Research T cell medicine.medical_treatment Immunology Uterine Cervical Neoplasms chemical and pharmacologic phenomena Adenocarcinoma CD8-Positive T-Lymphocytes T-Lymphocytes Regulatory Immune tolerance Immunoenzyme Techniques Carcinoma Adenosquamous Immune system Immune privilege Immune Tolerance medicine Humans Immunology and Allergy Cytotoxic T cell Organic Chemicals Lymph node Aged Aged 80 and over business.industry FOXP3 Forkhead Transcription Factors hemic and immune systems Dendritic Cells HLA-DR Antigens Immunotherapy Middle Aged Neuropilin-1 medicine.anatomical_structure Oncology Lymphatic Metastasis Carcinoma Squamous Cell Female Lymph Nodes business Immunologic Memory |
| Zdroj: | Cancer Immunology, Immunotherapy. 58:1363-1373 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-008-0646-7 |
| Popis: | We compared the immune system state in metastatic tumour draining lymph nodes (mTDLN) and metastasis free TDLN (mfTDLN) in 53 early stage cervical cancer patients to assess whether the presence of metastatic tumour cells worsen the balance between an efficacious anti-tumour and a tolerogenic microenvironment.The immune system state was measured by immunophenotypic and functional assessment of suppressor and effector immune cell subsets.Compared to mfTDLN, mTDLN were significantly enriched in CD4(+)Foxp3(+) regulatory T cells (Treg), which, in addition, exhibited an activated phenotype (HLA-DR(+) and CD69(+)). Treg in mTDLN were also significantly enriched in neuropilin-1 (Nrp1) expressing cells, a subset particularly potent in dampening T cell responses. mTDLN tended to be enriched in a population of CD8(+)Foxp3(+)T cells (operationally defined as CD8(+)Treg) that showed a suppressor potency similar to Treg under the same experimental conditions. Plasmacytoid dendritic cells (pDC) and myeloid DC (mDC) generally show distinct roles in inducing T cell tolerance and activation, respectively. In line with the excess of suppressor T cells, the ratio pDC to mDC was significantly increased in mTDLN. Immunohistochemical testing showed that metastatic tumour cells produced the vascular endothelial growth factor, a natural ligand for Nrp1 expressed on the cell surface of Nrp1(+)Treg and pDC, and therefore a potential mediator by which tumour cells foster immune privilege in mTDLN. Consistent with the overall tolerogenic profile, mTDLN showed a significant Tc2 polarisation and tended to contain lower numbers of CD45RA(+)CD27(-) effector memory CD8(+)T cells.The increased recruitment of suppressor type cells concomitant with the scarcity of cytotoxic type cells suggests that in mTDLN the presence of tumour cells could tip the balance against anti-tumour immune response facilitating the survival of metastatic tumour cells and possibly contributing to systemic tolerance. |
| Databáze: | OpenAIRE |
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