Plot showing non-essential (black) and essential (red) genes in melanoma cells, based on CRISPR/Cas9 screening.

Daniel Peeper

Functional oncogenomics for tumor & immunotherapy

Tumor heterogeneity, immune dysfunction and therapy resistance are among the most substantial challenges that limit durable benefit of cancer therapies. Using powerful function-based genomics, we screen for novel therapeutic targets to tackle those clinical problems.

We develop rational combinatorial cancer treatments, which target both cancer and immune cells, thereby simultaneously eliminating the patient’s tumor and harnessing the immune system. This has already culminated in new concepts that we are translating to the benefit of the patient.

On this page we’re sharing some of the highlights of our lab, news items, our research, team members and, if you scroll to the bottom, our vacancies.

PhD defense Sofía Ibáñez Molero

Congrats to Sofía Ibáñez Molero for excellently defending her PhD thesis on functional interactions between cancer and the immune system. She already published several interesting papers and has a few under review. Among Sofía's discoveries is the identification of mechanisms by which cancers protect themselves against the immune system. Thanks for your important contributions to the lab and best of luck in your postdoc!

New PD-1 regulator published by David in JITC

Congrats to David and collaborators for publishing this important study in JITC on a new regulator of both immune checkpoints PD-1 and CTLA-4: TMED. This transport protein was discovered in a genome-wide screen for novel factors governing cell surface PD-1 expression. TMED is amenable to small molecule inhibition and this finding therefore allows exploration of therapeutic intervention of immune checkpoint expression in cancer.

Peeperlab Retreat 2024

This year, we had our lab retreat in Malmedy (Belgian Ardennes). We had a very nice mix of science and leisure with bubble football, pubquiz, BBQ and quality time together. This is a special group of people, happy to be part of it.

Thanks all for organizing!

PhD degrees for Esmee and Disha

Congrats to Esmee Hoefsmit and Disha Rao for obtaining their PhD degrees, based on their very interesting studies on models, biomarkers, mechanisms and toxicity of immune checkpoint blockade for melanoma.

Well done and best of luck in your next career steps!

Lin, Levy, Alflen, Apriamashvili et al., Cancer Cell, 2024

Congrats to Chun-Pu, Pierre, Astrid and Georgi for publishing their wonderful joint and comprehensive study in Cancer Cell! They performed multimodal genome-wide CRISPR knockout screens in primary CD8 T cells for genes controlling fitness upon differential stimulation, identifying Dap5, Icam1, and Ctbp1, which are functionally annotated and characterized based on their unique or shared contribution to traits limiting T cell antitumor activity. Targeting these genes under relevant conditions could enhance T cell antitumor activity, for example in T cell therapies.

PhD defense David Vredevoogd

Congratulations to David Vredevoogd for receiving his PhD degree cum laude (with honors)! David, your thesis defense (Genetic screens to improve immunotherapy) was as excellent as your scientific achievements. Best of luck in your future career!

Peeperlab Retreat 2023

Wonderful Peeperlab retreat 2023 in Belgian Ardennes, with mix of science and leisure: SWOTs, brainstorming, playing pool, canoeing and quality time together. Thanks to the team for organizing!

Kenski, Huang, Vredevoogd et al., Cell Reports Medicine, 2023

In this paper, we show that whereas IDO1 inhibitors were developed to reinvigorate T cells by restoring tryptophan, they lack clinical benefit. We discovered an adverse effect of IDO1 inhibition: protecting melanoma cells from the effects of T cell-derived IFNγ. MITF plays a key role in this response in vitro and in patients.

Read the paper here.

Lin, Traets, Vredevoogd et al., The EMBO Journal, 2023

Immunotherapy resistance limits clinical benefit, urging a better mechanistic understanding of resistance pathways and discovery of new therapeutic targets. We have mined a genome-wide CRISPR-Cas9 screen performed previously and uncover TSC2 as a critical factor protecting tumor cells against cytotoxic T lymphocyte attack.

Read the paper here.

Zhang, Kong, Ligtenberg et al., Cell Reports Medicine, 2022

In a cover story, we identify by CRISPR-Cas9 knockout screening in tumor cells all components of the LUBAC linear ubiquitination complex: RNF31, SHARPIN, and RBCK1. Genetic or pharmacologic inhibition of RNF31 sensitizes tumors to both NK and CD8+ T cell killing by disrupting TNF receptor complex I signaling, while enhancing bystander killing.

Read the paper, see the news coverage by NKI and listen to the interview on BNR radio.

Apriamashvili, Vredevoogd et al., Nature Communications, 2022

The IFNγ response pathway is associated with response to immunotherapy in cancer. We reported in this paper that high levels of the IFNγ-receptor (IFNγ-R1) affect the outcome of immunotherapy in a context-dependent fashion and identify the E3 ubiquitin ligase STUB1 as a negative regulator of IFNγ-R1/JAK1 expression in cancer cells.

Read the paper, see the coverage by Oncode.

How can tumors circumvent the immune system

The development of immunotherapy has led to major advances in cancer care. Unfortunately, resistance to this type of treatment occurs in many patients at some point. The Peeper lab is conducting research to find out how resistance arises and what can be done to prevent or limit it. A better understanding of this problem is needed to improve immunotherapy. (Interview in Dutch)

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