ESMO 2025 | HLA loss, neoantigen fitness, and tumor mutational burden in cancer
Michael Gormally, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY, comments on the relationship between HLA loss of heterozygosity and tumor mutational burden, highlighting that the fitness of mutations to become neoantigens is a more important factor. Tumors with a higher burden of immunogenic neoantigens are more likely to exhibit HLA loss of heterozygosity, and while tumor mutational burden may be correlated with this phenomenon, it is not directly interlinked. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
How HLA loss of heterozygosity tracks with tumor mutational burden is definitely an open question. As far as we can tell, what’s more important is the fitness of the mutations to become neoantigens. So we’ve noticed that tumors that have a higher burden of immunogenic neoantigens, not necessarily just the overall tumor mutational burden, really predicts HLA loss of heterozygosity...
How HLA loss of heterozygosity tracks with tumor mutational burden is definitely an open question. As far as we can tell, what’s more important is the fitness of the mutations to become neoantigens. So we’ve noticed that tumors that have a higher burden of immunogenic neoantigens, not necessarily just the overall tumor mutational burden, really predicts HLA loss of heterozygosity. But of course, you know, when you have more hits on a tumor, a greater tumor mutational burden, it’s more likely that you would have that type of scenario. So they are probably correlated, but not directly interlinked.
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