Single-Cell Omics to Reveal Mechanisms of Response to Immunotherapy

PhD defense Amelie Franken

On Monday 15th of April, I will publicly defend my PhD thesis at 16:00 in Arenberg Castle, Heverlee.
You are most welcome to attend the defense and the reception afterwards!

Registration

Please register your attendance by March 29th, here. You can also use this form to indicate whether you would like to receive a printed copy of my dissertation.

Practical

The defense will take place in the auditorium located on the first floor of Arenberg Castle (01.07).

Convenient parking is available at Parking Kapeldreef, from which Arenberg Castle is only a 10-minute walk away.
You can enter the parking lot with access code 36488#.

Thesis and slides

My slides will be made available after the defense.

Synopsis

The quest for effective cancer treatments has led to the development of immune checkpoint blockade (ICB) therapy, revolutionizing cancer care by harnessing the patient's immune system to target cancer cells. However, despite its promise, many patients still struggle to achieve successful responses or face relapse after treatment. In response to this challenge, the combination of different agents, such as anti-PD-(L)1 plus anti-CTLA4, has emerged as a pivotal strategy. Yet, the efficacy of these combinations remains unclear, leaving unanswered questions about which patient subgroups would benefit the most.

To investigate the contribution of anti-CTLA4 to anti-PD-L1 therapy, we conducted a neoadjuvant window-of-opportunity study in head and neck squamous cell carcinoma (HNSCC). Leveraging cutting-edge single-cell and spatial technologies, we uncovered complimentary mechanisms underlying responses to anti-PD-L1+anti-CTLA4 combination therapy versus anti-PD-L1 monotherapy. Our discoveries paint a fascinating picture: patients who respond to anti-PD-L1 monotherapy often possess an already activated immune response prior to treatment, which is further amplified by the therapy. Conversely, the addition of anti-CTLA4 to anti-PD-L1 therapy triggers a novel immune response by activating CD4+ T-cells in tumor-draining lymph nodes, orchestrating their migration to the tumor site. These findings underscore the promise of combined anti-PD-L1+anti-CTLA4 therapy, particularly for patients initially resistant to anti-tumor immune activation.

In essence, our research unveils the complexities of ICB therapies, providing invaluable insights into their mechanisms and paving the way for tailored approaches to HNSCC treatment.