Research

Virus-associated carcinogenesis

For almost 20 years, our work has focused on human papillomavirus (HPV) infections and how the high-risk (carcinogenic) strains of these viruses persistently escape host immune responses, ultimately leading to the development of (pre)cancerous lesions in their host.

Despite numerous studies and discoveries over the past 40 years, and notably, the commercialization of vaccines covering several carcinogenic HPV types in the late 2000s, the field of HPV research continues to advance rapidly. This progress is driven by the more than 700,000 HPV-positive cancers still diagnosed each year worldwide, as well as many unresolved questions related to the viral life cycle and virus–host interactions.

Over the years, we modestly believe that our team has developed internationally recognized expertise, as evidenced by numerous publications (including some in high-impact, well-recognized journals; see publication list), more than 20 invited oral presentations abroad, and participation in numerous PhD thesis juries in Belgium and internationally (France, Switzerland, Luxembourg, the Netherlands). The main strength of our research group lies in the use of diverse technological approaches, such as whole-genome sequencing, binary interactome mapping, metagenomics, laser capture microdissection, organotypic raft cultures, and in vivo models, as well as in the analysis of multiple aspects of HPV biology. These range from molecular virology (with a focus on the viral E6/E7 oncoproteins) to antiviral immune responses, epidemiology, and histopathology, all aimed at addressing long-standing unresolved questions related to HPV infections.

Ongoing projects aim to (non-exhaustive list):

1. decipher the high susceptibility of uterine cervix for HPV infections (and related carcinogenesis)
2. characterize the hijacking of host DNA repair cascades by E6/E7 viral proteins (from both alpha and beta HPV genotypes)
3. characterize the initially infected cell (sub)population in a particular organ

Cancer immunotherapy using “second generation” immune checkpoint inhibitors

Over the past decade, immunotherapy using anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies has generated substantial interest for the treatment of patients with metastatic cancers or those unresponsive or resistant to targeted therapies or chemoradiation. Despite impressive clinical successes in certain cancer (sub)types, the overall response rate to anti-PD-1/PD-L1 inhibitors remains modest (less than 20%) across most malignancies. These population-based results clearly highlight the complexity of anti-tumor immunity and underscore the unrealistic expectation that a single immunotherapeutic agent will provide durable efficacy in all cancer patients. Indeed, anti-cancer immune responses are influenced by numerous factors, ultimately resulting in high variability in patient responses to treatment.

Building on our experience with anti-tumor immune defects (primarily studied in the context of HPV-positive neoplasms), we launched a new research theme in 2015, focused on cancer immunotherapy using “second-generation” immune checkpoint inhibitors targeting proteins other than PD-1, PD-L1, or CTLA-4. Notably, we have recently published our first articles on this new line of research in high-impact, well-recognized journals in the field (see publication list).

Ongoing projects aim to (non-exhaustive list):

1. analyze the therapeutic efficacy of "second generation" immune checkpoint inhibitors (e.g. anti-VISTA, anti-B7-H3, anti-CD200) (in the context of both basal-like breast cancer and advanced pleural mesothelioma)