Tumor antigens recognized by tumor-infiltrating lymphocyte T-cell receptors (TIL-recognized antigens)

Tumor antigens recognized by tumor-infiltrating lymphocyte (TIL) T-cell receptors (TCRs) represent a heterogeneous class of molecular targets presented on the surface of malignant cells via Major Histocompatibility Complex (MHC) molecules (Rosenberg & Restifo, 2015, Science). These antigens are broadly categorized into neoantigens, which result from unique somatic mutations within the tumor, and non-mutated self-antigens, such as cancer-testis antigens (e.g., MAGE-A4) or overexpressed differentiation antigens (Hinrichs & Rosenberg, 2014, Immunol Rev). TILs are naturally occurring immune cells that have infiltrated the tumor microenvironment in response to these specific signatures. In therapeutic applications, such as the FDA-approved Lifileucel (Amtagvi), TILs are harvested, expanded ex vivo, and re-infused into the patient to exploit their natural TCR-mediated recognition of these antigens (FDA, 2024). The interaction between the TCR and the antigen-MHC complex induces the release of cytotoxic granules like perforin and granzymes, leading to targeted tumor cell lysis. While this approach has shown significant efficacy in solid tumors like melanoma, therapeutic challenges include the identification of dominant neoantigens and the risk of on-target off-tumor toxicity if the targeted antigen is also expressed in healthy tissues.

Other names

NeoantigensTumor-specific antigens (TSAs)Tumor-associated antigens (TAAs)Cancer-testis antigens (CTAs)Shared tumor antigensMutation-derived antigens

Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) or TCR-engineered T-cells that specifically bind to peptide-MHC complexes on the surface of tumor cells, triggering cytotoxic T-lymphocyte mediated apoptosis and cytokine release.