ITOC 2026 | NOTUM’s role in immune evasion and tumor microenvironment interactions
Krijn Dijkstra, MD, PhD, Netherlands Cancer Institute, Amsterdam, Netherlands, comments on the potential role of the protein NOTUM in cancer immune evasion, noting that while NOTUM is a consistent hit across various data sets, its direct causal relationship with T-cells is still unclear. Experiments have not shown a direct effect of NOTUM on T-cells, suggesting it may work indirectly through other cells like fibroblasts or immune cells. This interview took place at 12th Immunotherapy of Cancer (ITOC) Conference in Munich, Germany.
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Transcript
I think by really overlaying all these different data sets, we can move from coincidental findings to consistent findings, and then this protein NOTUM really is the strong, consistent hit that we keep seeing coming back. Now, what we don’t know yet is whether this is a direct causal agent, right, whether NOTUM directly acts on T-cells. And to be honest, when we do experiments putting T-cells and cancer cells in addition to NOTUM, we don’t see much of an effect there...
I think by really overlaying all these different data sets, we can move from coincidental findings to consistent findings, and then this protein NOTUM really is the strong, consistent hit that we keep seeing coming back. Now, what we don’t know yet is whether this is a direct causal agent, right, whether NOTUM directly acts on T-cells. And to be honest, when we do experiments putting T-cells and cancer cells in addition to NOTUM, we don’t see much of an effect there. So it might work indirectly through additional cells like fibroblasts or other immune cells. So we don’t know yet whether this is a marker of immune-excluded cancers or a direct causal agent. But what it tells us is that the secretome is fundamentally altered in those tumors that escape from immune attack versus those that do.
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