(i) T cell trafficking to the brain (Calzascia 2003, 2008)

(ii) Identification of glioma antigens (Dutoit Brain 2012)

(iii) Therapeutic vaccines (Hilf Nature 2019, Migliorini Neuro oncol 2019)

A key step in the development of immunotherapy for glioma was the identification of a set of glioma antigens by the Dietrich group in 2012, and the initiation of several clinical trials based on these findings. These studies showed that CD4 and CD8 T cell responses to the vaccines can be elicited. Further approaches of combining these vaccines with other treatment modalities are currently being tested.

This identification of brain tumor antigens in our laboratory was directly translated into the clinic through a clinical trial of peptide vaccination using our targets, which started in Geneva in 2013. This vaccine, given to patients already suffering from the disease, specifically stimulates tumor-reactive T lymphocytes present in the patient’s blood that patrol the body to find and kill tumor cells. After having vaccinated 19 patients, we are now analyzing the immune responses elicited by the vaccine and are following the patients’ clinical evolution. This has provided us with important information to understand the effect of the vaccine on the patients’ immune system and disease. Importantly, a follow-up trial is currently ongoing at HUG, which combines the present peptide vaccine with (i) an anti PD1 antibody (pembrolizumab) that allows sustained activation of T cells, thereby improving vaccine efficacy, and (ii) a modulator of the microenvironment (TLR agonist). This work has led to the concept of personalized peptide vaccines and has allowed us to design better vaccines for patients suffering from glioma.

Rectal cancer is one of the ten most common cancers worldwide. Current curative treatment sequences use radiotherapy or chemoradiotherapy followed by surgery. Although curative, this combined approach is associated with important morbidity due to the loss of continence and an important risk of relapse. A major obstacle in the development of effective therapies is posed by the intrinsic and extrinsic biological heterogeneity of these tumors.

Our group focuses on studying the tumor immune microenvironment in rectal cancer and its modifications following radiotherapy or chemoradiotherapy with the aim to uncovering ways to harness it for therapy.

Currently, we are working on four different projects:

• Capturing cellular dynamics in rectal cancer using scRNA sequencing:

Our study aims at bridging this knowledge gap by generating a single-cell atlas of RC tumor cells and their surrounding immune and stromal cells, as well as exploring cell-specific transcriptional changes related to specific therapeutic interventions.

• Tackling immune exclusion in microsatellite stable rectal cancer:

By applying a combination of in vitro and in vivo rectal cancer models, ‘omics’ approaches and advanced imaging techniques, we aim at developing alternative approaches to promote de novo T cell activation and infiltration into the tumor microenvironment of microsatellite stable rectal cancer and other non-inflamed tumors.

• Breaking barriers to successfully treat rectal cancer - a clinical trial:

Our clinical trial (PEMREC) is the first study evaluating a novel therapeutic approach that combines radiotherapy with an anti-PD1 antibody. This study could lead to a major breakthrough in the treatment of rectal cancer.

• Explore functional states and spatial interactions between cell types using multiplexed-IF and advanced image analysis:

Here, we aim at developing a multiplexed immunofluorescent technology to FFPE tissue along with a software for digital pathology to characterize the tumor microenvironment of rectal cancer.