What we do
About our project
Motivation
To better understand how tumor cells adversely affect numbers, localization and function of (subsets of) T cells.
Charting T cell immunity both in tissues and blood is expected to provide indicators for clinical response to immune therapies, as well as identiy shortcomings in T cell immunity to enable the selection of drugs to target these shortcoming to sensitize the tumor to the host immune system.
Our aim
Our aim is to interrogate tumors and blood of cancer patients for their immune profile, particularly T cell profile, and identify dominant evasive mechanisms. In doing so, we intend to be better able to define the most optimal (combination) therapy for patients.
Performance
T cell profiling is performed with different types of samples and multiple techniques.
- mRNA: assessment of frequencies of immune cell populations, and differential expression of genes and occurrence of pathways
- tissues: multiplex immune fluorescence stainings using Vectra 3.0
- blood and single tumor cell suspensions: flow cytometry using FACSCelesta
The high dimensional data generated by above techniques are analyzed using biased and unbiased machine learning algorithms.
The TME facility includes the Vectra 3.0 and Leica Bond, and has available expertise and panels to interrogate T cell immunity in tumor tissues. Coordinator is dr. Emrah Bacioglu.
Outcome
The identification of dominant T cell evasive mechanisms that are either pan-cancer (occurring in multiple tumor types) or specific for certain tumor(subtypes), and the selection of (combination) treatments in a rational manner.
We have recently reported on T cell immunity in breast cancer (tissues) as well as non-small cell lung cancer (blood). We are currently extending our T cell profiling to multiple other tumor types, such as sarcoma, oral cavity carcinoma, bladder cancer, pancreas cancer, and multiple myeloma (see publications).
Funds & Grants
- Dutch Cancer Society; EMCR 2014-7087; Cranking up tumor-specific T cell responses in metastatic breast cancer. PI: Debets R; co-PI: Martens J: 460 k€.
- Erasmus MC Daniel den Hoed Foundation, 2017; Tumor Micro-Environment Screening Center. PI: Debets R. 600 k€.
- Merck, 2017; Genomic and immune profiling of metastasized urothelial cancers. PI: Lolkema M; co-PIs: Debets R, de Wit R. 110 k€.
- Stichting Zabawas/overleven met alvleesklierkanker, 2019; Meten en visualiseren van immuuncellen in alvleesklierkanker: ‘state-of-the-art’ techniek om therapiekeuze te verbeteren. PI: Debets R. 94 k€.
- Erasmus MC Daniel den Hoed Foundation, 2019; Adoptive T cell therapy to treat common cancers: new roads to unique targets and pre-treatments. PI: Debets R. 500 k€.
Publications
- CD45RA+CCR7- CD8 T cells lacking co-stimulatory receptors demonstrate enhanced frequency in NSCLC patients responding to nivolumab.
- Clonality, antigen recognition and suppression of CD8+ T cells differentially affect prognosis of breast cancer subtypes. Clinical Cancer Research
- Differential quantities of immune checkpoint-expressing CD8+ T cells in soft tissue sarcoma subtype. J Immunotherapy Cancer, under revision.
- Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T-cell evasion in triple negative breast cancer. Can Disc, under review.
- Response of metastatic urothelial cancer to anti-PD1 treatment is characterized by recruitment and activation of CD4 T cell subsets. Manuscript in preparation.
- TME-Analyzer: A multi-dimensional visualization and analysis tool to capture immune contexture in tumor tissues. Manuscript in preparation.
Our team
- Reno Debets, PhD, prof, principal investigator
- Emrah Balcioglu, PhD, postdoctoral fellow
- Dora Hammerl, MSc, PhD student
- Maud Rijnders, MD, PhD student
- Chumut Phanthunane, MSc, PhD student
- Rebecca Wijers, BSc, research technician B
- Astrid Oostvogels, BSc, research technician A
Contact us? Mail to
Contact TME-facility? Mail to
