A research team has identified the basis for tumor-infiltrating lymphocyte (TIL) therapy for ovarian cancer. Published in SCIENCE CHINA Life Sciences, the study reveals that TCF7-expressing T cells with autologous tumor reactivity are effectively expanded ex vivo.
Despite FDA approval for melanoma, TIL therapy against ovarian cancer is still under investigation. Using paired scRNA/TCR-seq analysis of patient-derived TILs, the researchers discovered that three tumor-reactive TCF7+ T cell subpopulations exhibit selective expansion during TIL production, including CD8+ TCF7+ Tpex, TCF7+GZMK+ early Tem and CD4+ TCF7+ Tfh cells. Crucially, CD8+ TCF7+ Tpex cells demonstrate self-renewal capacity and generate stem-like progenies. Furthermore, the team found that CCR7 and CD200 co-expression identifies tumor-reactive T cells with optimal therapeutic potentials. Targeting tumor-infiltrating CCR7+CD200+ T cells enriches stem-like, tumor-reactive T cells, which may promote the persistence and tumor specificity in current TIL therapy.
These findings suggest actionable strategies for next-generation TIL therapies.
Journal
Science China Life Sciences
Method of Research
Experimental study