Tumor-associated peptide-Human Leukocyte Antigen complex (pHLA) (pHLA)

Tumor-associated peptide-Human Leukocyte Antigen (pHLA) complexes are molecular assemblies presented on the surface of malignant cells, comprising a short peptide fragment derived from a tumor-associated antigen (TAA) or neoantigen bound within the groove of an HLA molecule (PMID: 30104441). These complexes are the fundamental targets for the T-cell receptors (TCRs) of Tumor-Infiltrating Lymphocytes (TILs), which are naturally occurring immune cells that have migrated into the tumor microenvironment (PMID: 31611556). In the context of cancer, these complexes represent non-self or altered-self signals that, when recognized by TCRs, trigger a cascade of T-cell activation, proliferation, and cytotoxic activity against the tumor cell (Nature Reviews Immunology, 2019). Therapeutic interventions such as TIL therapy (e.g., lifileucel) and TCR-engineered T-cell therapies (e.g., afamitresgene autoleucel) leverage this recognition mechanism to achieve tumor regression (FDA, 2024). The specificity of this interaction is determined by both the specific peptide sequence and the patient's HLA genotype, making it a highly personalized target (PMID: 29970717). However, therapeutic efficacy can be hindered by tumor-mediated downregulation of HLA expression or the development of antigen-loss variants (PMID: 29650591). These complexes are also the focus of TCR-bispecific molecules, which bridge T cells to tumor cells by binding the pHLA complex (PMID: 35082431).

Other names

Peptide-MHC complexpMHCTumor-associated antigen-HLA complexNeoantigen-HLA complexTAA-HLA complex

T-cell receptor-mediated recognition of peptide-HLA complexes on tumor cells, triggering cytotoxic T-lymphocyte activation and subsequent tumor cell lysis.