Deciphering the immune response against human papillomavirus infection using imaging mass cytometry
Human papillomaviruses (HPVs) are responsible of approximately 5% of cancers worldwide, in particular cervical cancer in women. They are also responsible of recalcitrant warts, and devastating benign tumors such as Buschke-Lowenstein tumor and tree man syndrome. Patients with immunodeficiencies, either inherited or acquired, are at increased risk of developing HPV-driven diseases. Despite the burden of HPVs in human health, the immune response against HPV remains poorly understood. In particular, the immunological infiltrate in regressing warts was never characterized due to the difficulty to get access to the samples and technological limitations. The novel high dimension technologies applied to tissular analysis offer unique opportunities to fill this important gap of knowledge. We developed a panel of 35 antibodies for imaging mass cytometry (Hyperion technology, Fluidigm) to study in great depth the immunological infiltrate in the regressing warts.
In this context, we are recruiting primary immunodeficiency patients with extensive warts (such as DOCK8, CARMIL2 and GATA2 deficiencies), and scheduled for hematopoietic stem cell transplantation. We will take biopsies of one lesion and healthy skin prior transplantation (e.g. during catheter placement) and one biopsy after transplantation during the regression of the lesions. Blood samples will be sampled during regression, one month and 6 months after regression to assess anti-HPV response in circulating lymphocytes. Altogether, this study will be the first in depth characterization of human peripheral and in situ anti-HPV responses.
The knowledge acquired from this study will benefit all patients with HPV-driven diseases and may pave the way for novel therapeutic approaches.
Romain Lévy :
Laboratory of human genetics of infectious diseases
INSERM U1163, Institut Imagine
24 Bld du Montparnasse
75015 Paris, France