Tumor-specific mutant peptides that T cells can recognize–the targets of anti-tumor immunity.
The success of checkpoint immunotherapy depends on pre-existing anti-tumor T cells that recognize neoantigens. Checkpoint blockade doesn't create new T cell responses–it unleashes existing ones that were suppressed.
This explains why highly mutated tumors (high TMBLoading..., MSILoading...-H) respond better to immunotherapy: more mutations generate more neoantigens, increasing the probability that immunogenic peptides exist.
What They Are: Neoantigens are abnormal proteins created by tumor mutations. Because they're "foreign" (not present in normal tissue), the immune system can potentially recognize and attack them.
Why They Matter: More neoantigens = more immune targets. This helps explain why highly mutated tumors (like MSI-high) respond better to immunotherapy.
Neoantigen quality matters as much as quantity. Factors determining immunogenicity include: MHC binding affinity, similarity to self-peptides, clonal vs. subclonal expression, and the specific TCR repertoire of each patient.
This complexity explains why TMB/MSI are imperfect predictors–they measure neoantigen load but not immunogenicity or whether checkpoint suppression prevents T cell function. Functional biomarkersLoading... measuring checkpoint engagement capture this missing information.
Not Just Numbers: Having many neoantigens doesn't guarantee response. The immune system must see them (MHC presentation) and act on them (not blocked by checkpoints).
The Integration: Neoantigen load tells you about potential targets. Functional checkpoint measurement tells you whether immune suppression is blocking the response to those targets.
