CD4-positive tumor-infiltrating lymphocyte (CD4+ TIL) (CD4+ TIL)

CD4-positive tumor-infiltrating lymphocytes (CD4+ TILs) are a heterogeneous population of T helper cells found within the stroma and parenchyma of solid tumors (Borst et al., 2018, Nature Reviews Immunology). These cells play a pivotal role in the immune microenvironment, acting as coordinators of the anti-tumor response by secreting cytokines like interferon-gamma and providing essential help to CD8+ cytotoxic T cells (Tay et al., 2021, Nature). However, the population also includes regulatory T cells (Tregs) that express FoxP3 and function to suppress immune activity, thereby promoting tumor progression and therapy resistance (Ohue & Nishikawa, 2019, Cancer Science). In the context of modern oncology, CD4+ TILs are utilized in adoptive cell therapy, where they are extracted from a patient's tumor, expanded to large numbers in a laboratory, and re-infused to overwhelm the cancer (FDA, 2024, Amtagvi Approval). Drugs such as lifileucel represent this approach, while other therapies like checkpoint inhibitors target receptors on these cells to prevent exhaustion and maintain their effector capacity (Waldman et al., 2020, Nature Reviews Immunology). The presence and composition of CD4+ TILs are often used as prognostic indicators, with a high ratio of effector T cells to regulatory T cells generally correlating with better clinical outcomes (Paijens et al., 2021, Nature Reviews Clinical Oncology). Safety concerns associated with manipulating these cells include systemic inflammatory responses and potential autoimmunity if the cells recognize self-antigens (June et al., 2018, Science).

Other names

CD4+ tumor-infiltrating T cellTumor-infiltrating CD4+ T lymphocyteCD4+ TILs

Adoptive cell transfer (ACT) involving ex vivo expansion and re-infusion; modulation of effector function via immune checkpoint blockade (e.g., PD-1/CTLA-4 inhibition).