Targeting of cytokine secreting lymphocytes (TCSL)

The mission of our research is to dissect the role of innate lymphoid cells (ILCs) and tumor-specific CD4 T cells in human anti-tumor immunity, to optimize current immunotherapy strategies. 

Targeting human ILCs to reinvigorate anti-tumor immunity

As innate and rapid source of distinct cytokines, Innate Lymphoid Cells (ILCs) have emerged as key orchestrators of immunity, inflammation and homeostasis. We are interested in examining the roles of ILCs in human anti-tumor immunity. By multiparametric flow cytometry we are assessing quantitative and qualitative alterations of ILCs directly in cancer patients. Using ex-vivo ILCs and short-term in vitro expanded ILC lines we are dissecting the cross-talk between ILCs and adaptive immune cells, myeloid, endothelial and cancer cells. By interfering in vitro and in vivo with identified targetable pathways we are exploring therapeutic options that exploit ILC biology, in particular (i) adjuvants’ optimization targeting ILC subsets that favour tumor rejection (ii) the use of ILC lines expanded in vitro as cell therapy based approaches, (iii) the use cytokines, small molecular compounds and epigenetic regulators that may promote expansion and/or reprogramming of endogenous ILCs in cancer patients.

High-throughput analysis of tumor-specific CD4 T cells for cancer immunotherapy

Increasing evidence highlights the crucial roles of CD4 T cells in anti-tumor immunity. We focus on the quantitative and qualitative analyses of natural and vaccine-induced tumor-specific CD4 T cell responses. By adopting a high-throughput, HLA-independent, T cell library approach we interrogate CD4 T cells specific for a wide range of human tumor-associated antigens, including neoantigens, in terms of frequency, phenotype, TCR usage, fine specificity and persistence longitudinally during cancer patients’ treatment.

In collaboration with Pr. George Coukos’ tetramer platform, we are optimizing next-generation peptide-MHC Class II multimers to identify, isolate and characterize multiple tumor-antigen specific CD4 T cells from small biological samples. We are gaining insights into TCR-pMHC interactions and function of tumor-specific CD4 T cells in order to select optimal TCRs for sequencing and cloning. These reagents could then be used to transfect or transduce CD4 and CD8 T cells for adoptive cell transfer therapy.

Dissecting the spatial organization of the tumor microenvironment for optimized immunotherapy

The tumor microenvironment is a mixture of different cells, comprising malignant, immune, vascular and stromal cells. Despite the apparent intratumoral chaos, recent evidence shows an unexpected high degree of spatial organization within tumors. We are combining in vitro experimental approaches, mathematical modelling and knowledge gained from models of microbial communities (in collaboration with Prof S Mitri), to decipher how multicellular organization is established within tumors. The disruption of key processes underlying tumor organization might represent novel targets to exploit therapeutically.

Neuro-immunology as a new target in racial bias, and beyond

Self-other differentiation is a central concept of the immune system (biological immune system), but it is also a key function of the central nervous system, guiding everyday’ behavioral responses (behavioral immune system). However, it is currently unknown whether and how the biological and the behavioral immune systems interact with each other. To gain this knowledge, we are presenting to healthy individual potentially threatening stimuli, administered through virtual reality (RealiSM system) and we are monitoring psychophysical, electrophysiological and immunological parameters (in collaboration with Prof A. Serino). Moreover, we are testing whether it is possible to modulate the behaviorally-mediated immune responses via specific cognitive manipulations, that might be exploited for therapeutic purposes in the context of racial bias, but also allergic disorders or even cancer.

• Trabanelli S., Chevalier MF., Martinez-Usatorre A., Gomez-Cadena A., Salomé B., Lecciso M., Salvestrini V., Verdeil G., Racle J., Papayannidis C., Morita H., Pizzitola I., Grandclément C., Bohner P., Bruni E., Girorta M., Pallavi R., Falvo P., Leibundgut EO., Baerlocher GM., Carlo-Stella C., Taurino D., Santoro A., Spinelli O., Rambaldi A., Giarin E., Basso G., Tresoldi C., Ciceri F., Gfeller D., Akdis CA., Mazzarella L., Minucci S., Pelicci PG., Marcenaro E., McKenzie ANJ., Vanhecke D., Coukos G., Mavilio D., Curti A., Derré L.* and Jandus C.* Tumor-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis. *: equal contribution Nat Commun 2017 Sep, 8(1):593
   
• Chevalier MF., Trabanelli S., Racle J., Cesson V., Gharbi D., Domingos-Pereira S., Dartiguenave F., Fritschi A-S., Speiser DE., Rentsch CA., Gfeller D., Jichlinski P., Nardelli-Haefliger D., Jandus C.* and Derré L.*, Local T-cell to MDSC balance is modulated by group-2 innate lymphoid cells and predictive of bladder cancer recurrence. *: equal contribution. J Clin Invest 2017 Aug, 127 (8):2916-2929
   
• D., Romano E., Michielin O., Romero P., Speiser DE.* and Jandus C.* Vaccination of stage III and IV melanoma patients with long NY-ESO peptide and CpG-B elicits robust CD8 and CD4 T-cell responses with multiple specificities including a novel DR7 restricted epitope. *: equal contribution. Oncoimmunology, 2016 Sep, 5(10):e1216290
   
• Trabanelli S., Curti A., Lecciso M., Salomé B., Riether C., Ochsenbein A., Romero P. and Jandus C. CD127⁺ innate lymphoid cells (ILCs) are dysregulated in treatment naïve acute myeloid leukemia (AML) patients at diagnosis. Hematologica 2015 Jul, 100 (7): e257-60
   
• Scholz G., Jandus C., Zhang L., Grandclement C., Dormond-Meuwly A., Lopez-Mejia IC., Soneson C., Delorenzi M., Fajas L., Held W., Dormond O. and Romero P. Modulation of mTOR signalling triggers the formation of stem-cell like memory T cells. EBiomedicine 2015

• SNSF PRIMA fellowship
• SNSF Swiss-Indo Joint Programm
• Krebsliga Schweiz (KLS)
• FBM interdisciplinary grant UNIL
• SAV-Fonds Novartis Consumer Health
• Fondation MEDIC
• Olga Mayenfish Stiftung
• Helmut Horten Foundation
• Swisslife (to Dr S. Trabanelli)
• ProFemmes UNIL fellowship (to Dr S. Trabanelli)