TIL Therapy and Neoantigens: How Tumor-Infiltrating Lymphocytes Recognize Mutations
By Lociven · NeoantigenLab · July 2026 Figure 1. TIL manufacturing timeline (left) and neoantigen-reactive TIL frequency by tumor type (right). TIL Therapy Series · Part 1 of 2 When Iovance's lifileucel received FDA approval in 2024 for metastatic melanoma, it validated TIL therapy as a viable commercial modality. But understanding why TIL therapy works — and why it sometimes doesn't — requires understanding the relationship between tumor-infiltrating lymphocytes and neoantigens. This post explains how neoantigens shape the TIL compartment, what neoantigen-reactive TILs look like functionally, and what this means for TIL expansion protocols. What TILs are and where they come from Tumor-infiltrating lymphocytes are T cells (predominantly CD8+, but also CD4+) found within the tumor microenvironment. They are not randomly distributed — they are shaped by the antigens present in the tumor, including neoantigens. When a somatic mutation generates a neoantige...