Image showing a cancer cell (red) conjugated to two active T cells (small blue cells) that are connected by an antigen-presenting cell (image made by Ella Maru studios).

Daniel Peeper

Translating the cancer-immune dialogue

Tumor heterogeneity, immune dysfunction and therapy resistance are among the most considerable challenges that limit durable benefit of cancer therapies. Despite the transformative impact of cancer immunotherapy, the majority of patients do not achieve durable clinical benefit. The overarching goal of our research is, therefore, to understand the biological mechanisms that limit immunotherapy efficacy, and to identify novel therapeutic vulnerabilities that can be exploited to improve patient outcomes.

Our research is built on the premise that advancing immunotherapy requires us to translate the dialogue between cancer and the immune system. We use translation in both senses of the word. First, we aim to decipher the molecular language governing interactions between tumor cells and immune cells. Second, we seek to translate these mechanistic insights into innovative therapeutic strategies that enhance anti-tumor immunity, overcome resistance and broaden the clinical benefit of immunotherapy.

To achieve these goals, our laboratory addresses three fundamental questions:

What tumor-intrinsic mechanisms drive resistance to immune-mediated killing, and how can they be therapeutically targeted?
What molecular pathways underlie T cell dysfunction within the tumor microenvironment, and how can effective anti-tumor immunity be restored?
How do functional interactions between cancer cells and immune cells shape therapeutic responses, and how can these interactions be leveraged to develop next-generation immunotherapies?

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.

Highlights

Important discovery published in Cancer Research

Congrats to Thijs & co-workers for publishing their important discovery in Cancer Research! By unbiased genetic screening, they found that targeting TDP2 or DNA-PKcs synergizes with low-dose doxorubicin to induce p53-mediated senescence. This also caused sensitivity to senolytics in MDM2-amplified liposarcoma, meriting therapeutic exploration. This work was co-led by Winan van Houdt and supported by RADAR.

Peeperlab Retreat 2026

^{May 2026}

This year, we returned to Belgium for another wonderful Peeperlab Retreat. We enjoyed a great mix of science and fun activities, with plenty of time to connect as a team. Scientifically, we dove into Night Science - the creative side of developing new ideas and hypotheses - which sparked many inspiring discussions. Grateful to be part of such a special group of people. Big thanks to everyone who helped organize it!

Our T cell clusters published in Nature

^{January 2026}

Huge congrats to shared first authors Sofia and Johanna, and all collaborators, for publishing our findings in Nature. They discovered a population of T cells with potent anti-cancer activity that has been commonly overlooked. These T cells reside in heterotypic cell clusters that can be readily isolated from clinical cancer specimens. Their findings could pave the way for improving TIL therapy, an avenue we have already begun to pursue.

PhD student Tim Arnoldus in Nature Genetics

Peeperlab Retreat 2025

PhD defense Sofía Ibáñez Molero

^{January 2025}

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

^{November 2024}

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

PhD degrees for Esmee and Disha

Comprehensive Cancer Cell Study Identifies New Targets to Enhance T Cell Anti-Tumor Activity

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

PhD defense David Vredevoogd

NWO Veni Fellowship

Peeperlab Retreat 2023

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.

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

Read the paper here.

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

3M€ NWO-XL grant awarded!

^{Augustus 2022}

Daniel Peeper and his colleagues Karin de Visser and Maarten Altelaar have obtained a prestigious 3M€ grant, entitled “interacT:T”, from NWO. They will use advanced techniques to study in great detail the interactions between tumor cells and T cells, with implications for immunotherapy.

ERC Advanced grant awarded!

^{April 2022}

Daniel Peeper was awarded with 2,5M€ ERC Advanced grant. His group will investigate how we can improve immunotherapy for cancer patients. With these highly competitive grants, the European Research Council supports groundbreaking projects by established research leaders.

Daniel Peeper celebrates 25-year anniversary at NKI

^{October 2021}

On a cold night in Boston almost thirty years ago, after yet another failed experiment, Daniel Peeper – head of the Division of Molecular Oncology & Immunology– considered changing careers. But a spark of inspiration the following morning changed his mind. Daniel has officially been working at the Netherlands Cancer Institute for twenty-five years. A great occasion for a conversation about his highs and lows, luck, and the perks of jumping into the unknown…

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

Rational Cancer Treatment Combinations: An Urgent Clinical Need

Technological innovations uncovered numerous new therapeutic targets. Some 5,000 clinical trials are probing the clinical benefit of urgently needed new combination treatments. However, the possibilities to combine individual treatments dramatically outnumber the patients available to enroll in clinical trials. This comes at a potential cost of missed opportunities, clinical failure, avoidable toxicity, insufficient patient accrual, and financial loss.

Researchers find way to outwit tumor cell

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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