γδ T lymphocytes, promote cervical cancer caused by the papillomavirus.
Dans la revue PNAS
A joint study by ULiège (GIGA) and ULB, published in PNAS, shows that a population of cells of the immune system, γδ T cells, could have an important effect in human papillomavirus-induced (HPV) cervical cancer, the third leading cause of cancer death in women.
Researchers from the GIGA Cellular and Molecular Immunology Laboratory (led by Nathalie Jacobs) and ULB's Pharmacotherapy and Pharmaceutical Pharmacy Department (led by David Vermijlen) have investigated unconventional T lymphocytes , cells expressing a receptor composed of γ and δ chains, in the specific case of human papillomavirus-induced (HPV) cervical cancer.
Of all tumor-infiltrating leukocytes, T cells bearing γδ T cell receptors have been associated with the most favorable prognosis. However, we show here, in a mouse model of carcinogenesis induced by human papillomavirus (HPV)-oncoproteins, that γδ T cells promoted the development of HPV-induced lesions.
Indeed, HPV-oncoprotein expression induced an infiltration of γδ T cells producing IL-17A, a proangiogenic cytokine, and a decreased density of anti-tumor Vγ5+ γδ T subsets. Supporting the clinical relevance of our observations, IL-17A+ γδ T cells were detected in human cervical cancer, where HPV-oncoproteins are highly expressed, but not in less advanced cervical lesions.
These results support the notion that viral oncoproteins can induce a switch from antitumoral to pro-tumoral γδ T subsets in solid tumors.
To better understand
Lymphocyte Cell in the immune system responsible for specific immunity. Lymphocytes are present in the blood (they constitute 25 % of white blood cells in adults) and in lymphoid organs (bone marrow, thymus, lymphatic ganglions, spleen, tonsils, etc). There are two categories of lymphocytes that differ according to their function. The T lymphocytes, which depend on the thymus, are responsible for cellular immunity. After activation, they can kill other living cells and produce factors that play a central role in the body’s immune response. The B lymphocytes depend on the bone marrow and, by producing antibodies, ensure humoral immunity.
• Nathalie JACOBS, Cellular and molecular immunology, Université de Liège (ULiège), Avenue de l'Hôpital, 3, 4000 Liège I +32(0)43662420 I firstname.lastname@example.org
• David VERMIJLEN, Institute for Medical Immunology (IMI),Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), 1050 Bruxelles I +32(0)26505295 I email@example.com
Or through the press offices : ULiège (04/366 52 11) / ULB (02/650 92 03)
‘Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation’, PNAS, Proceedings of the National Academy of Sciences of the United States of America, Online Early Edition, 09/10/2017, 3 :00 PM US Eastern Time.
Dorien Van hedea b, Barbara Polese c, Chantal Humblet a, Anneke Wilharm d, Virginie Renoux a, Estelle Dortu e, Laurence de Leval f, Philippe Delvenne e, Christophe Desmet a, Fabrice Bureau a, David Vermijlen b,1 , Nathalie Jacobsa 1
a Giga-Research / Cellular and molecular immunology / University of Liège
b Department of Pharmacotherapy and Pharmaceutics - Institute for Medical Immunology, Université Libre de Bruxelles (ULB)
c Giga-Research/ Laboratory of immunoendocrinology / University of Liège
d Institute of Immunology (OE5240), Hannover Medical School,
e Giga-Research/Experimental Pathology / University of Liège
f Pathologie Clinique / Institut Universitaire de Pathologie, Lausanne
This work results from the subject of the doctoral thesis of Dorien Van hede realized in co-tutelle ULiège (GIGA) and ULB.
Nathalie Jacobs is associate professor in Virology and Immunology since 2012. She a biologist with a PhD in Sciences form the University of Liège. Her PhD on immunotherapy against tumours was partially done in Experimental Oncology Lab of the istituto Nazionale dei Tumori in Milano (Embo fellow). She also worked during 2 years (Wellcome Trust senior postdoc) on the immune response against vaccinia virus in the Virology department at Imperial College of London. Back in Belgium, she obtained a position of research associate of FRS-FNRS in 2006 and developed her research group in the laboratory of Experimental Pathology. Her group joined the laboratory of Cellular and Molecular immunology in 2013 and her current research interest is the role of innate lymphocytes in anti-viral immune response.