Tumor-specific neoantigen–MHC–T cell receptor immune axis (Neoantigen-MHC-TCR axis)

The tumor-specific neoantigen–MHC–T cell receptor (TCR) immune axis is a tripartite interaction that serves as the cornerstone of precision immuno-oncology (Schumacher & Schreiber, 2015). This axis comprises a neoantigen (a peptide derived from a tumor-specific somatic mutation), a Major Histocompatibility Complex (MHC) molecule that presents the peptide, and a cognate TCR on the surface of a T lymphocyte (Blass & Ott, 2021). Because neoantigens are absent from the normal human genome, this axis provides a highly specific target for the immune system to distinguish malignant cells from healthy tissue, thereby minimizing off-target effects (Sahin & Türeci, 2018). Therapeutic strategies leveraging this axis include personalized neoantigen vaccines, which prime the endogenous T cell repertoire, and adoptive TCR-T cell therapies, which involve the infusion of T cells engineered with high-affinity receptors for specific neoantigen-MHC complexes (Hu et al., 2021). Despite its potential, the efficacy of targeting this axis is often challenged by the loss of HLA expression in tumor cells, low mutational burden in certain cancers, and the presence of an immunosuppressive tumor microenvironment (Yarchoan et al., 2017). Understanding the dynamics of this axis is critical for developing next-generation immunotherapies that can overcome tumor resistance mechanisms.

Other names

Neoantigen-HLA-TCR complexTumor-specific antigen-MHC-TCR axisNeoepitope-MHC-TCR interactionMutation-derived antigen-MHC-TCR axis

The mechanism involves the specific recognition of somatic mutation-derived peptides (neoantigens) presented by MHC Class I or II molecules by the T cell receptor (TCR), which triggers an intracellular signaling cascade leading to T cell activation, cytokine release, and targeted lysis of the tumor cell (Schumacher & Schreiber, 2015).