The Immunology Podcast

Ep. 126: “Functional Oncogenomics” Featuring Dr. Daniel Peeper

Mar 10, 2026
Guest
Daniel Peeper
Dr. Daniel Peeper, a leader in functional oncogenomics at the Netherlands Cancer Institute, uses genome-wide functional screens to find ways to overcome tumor heterogeneity and therapy resistance. He discusses melanoma resistance to BRAF inhibitors, decoding tumor–immune communication, screens that reveal interferon-gamma and TNF pathway roles, and strategies for genetically enhancing T cells and rational combination therapies.
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INSIGHT

Lab Pivot From Oncogenes To Immunotherapy Resistance

  • Daniel Peeper reframed his lab from cancer cell biology to immunotherapy resistance after seeing early checkpoint blockade success and anticipating future resistance problems.
  • He learned immunology from scratch, recruited immunologists, and shifted focus proactively to study mechanisms of immunotherapy resistance.
ANECDOTE

Conference Applause Sparked Lab Direction Change

  • Daniel recalls attending a melanoma conference where the first combo checkpoint results caused a spontaneous round of applause, marking a watershed moment in immunotherapy.
  • That experience motivated him to pivot his research toward anticipating resistance to these therapies.
INSIGHT

CRISPR Screens Reveal Causal Immune Resistance Genes

  • Functional genomics screens (CRISPR knockout/activation) establish causality by perturbing every gene and measuring effects on tumor sensitivity to T cell killing.
  • Peeper's lab transduces tumor cells with genome-wide libraries, challenges with T cells, sequences surviving guides, and identifies enriched/depleted hits for mechanistic and translational targets.
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