Postdoc vacancy in Peeper Lab - Breaking cancer immunotherapy resistance

The Netherlands Cancer Institute (NKI)
Located in Amsterdam, NKI is the only comprehensive cancer center in The Netherlands. It is
a well-organized and dynamic institute accommodating over 50 research groups and many
advanced core facilities. It is an internationally renowned center dedicated to fundamental,
translational and clinical cancer research.

Project information
The Peeper lab uses functional oncogenomic and other advanced technology to combat
immunotherapy resistance. The introduction of ICB, most commonly in the form of CTLA-4 and
PD-1 antibodies but also other therapies like TIL and CAR-T, has been clinically transformative.
However, most patients fail to respond (durably), often because of upfront or acquired
resistance. Several resistance mechanisms have been described, including tumor cell-intrinsic
and T cell-dependent ones. To develop therapeutic solutions, it is imperative that we
understand the underlying mechanisms. Furthermore, given the diversity of this problem, there
is a need to find specific solutions. Here, we focus on a therapeutic strategy to break tumor
cell-intrinsic immune resistance.

We have recently uncovered a critical and conserved mechanism of tumor cell-intrinsic
resistance involving TNF-mediated survival signaling. By genetic screening, we discovered that
ablation of TRAF2, a key TNF signal transducer sharply lowered the tumor TNF cytotoxicity
threshold, thereby augmenting tumor T cell- and ICB-impact in vitro and in preclinical murine
models. Furthermore, loss of TRAF2 in patient tumors increases immune sensitivity, which was
independently confirmed in a large-scale genetic analysis of clinical specimens. In this project,
we focus on a druggable target in this pathway that we have discovered, aiming to not only
understand its mechanism of action but also to explore clinical translation.

We are seeking a highly ambitious postdoc with a strong background in molecular and/or
cancer biology and immunology, experience with mouse studies, and an interest in fundamental
and translational cancer research. Your responsibilities will include writing of manuscripts and
grant applications. Proficiency in English and good communicative skills are important
requirements, as is a team player mentality.

The vacancy is available immediately. You will be employed for a minimum period of 2 years.
The gross salary per month is € 3.879 to € 4.611 according to salary scale FWG 55, depending
on your experience. The terms of employment will be in accordance with FWG 55 of the CAO
Ziekenhuizen (Collective Labour Agreement for Hospitals). In addition, you will receive a fixed
end-of-year bonus in December (8,33%) and in May you will receive 8,33% holiday pay.

Interested?
For further information and applications, please visit: https://www.nki.nl/research/research-groups/daniel-peeper/.
Applications should include your CV, a motivation letter and references. Apply by the 'Apply now' button at the bottom of the page. 

The NKI values diversity and is committed to creating an inclusive work environment that stimulates the best in each individual. Applications of all individuals are welcomed regardless of age, ancestry, religion, disability, distance from the labor market, sexual orientation or gender identity.

Select reading
- Vredevoogd et al., Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold,
Cell 2019
- Zhang et al, RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells,
Cell Reports Medicine 2022
- Boshuizen et al., Rational Cancer Treatment Combinations: An Urgent Clinical Need, Mol Cell 2020
- Boshuizen et al., Reversal of pre-existing NGFR-driven tumor and immune therapy resistance, Nature
Comm 2020