Speaker
Description
High-grade serous ovarian cancer (HGSC) almost always relapses after first-line treatment, yet how long patients remain progression-free varies enormously. One plausible explanation is that the immune state at the end of chemotherapy — in particular, how many memory T cells survive treatment — shapes the pace of tumour regrowth. Whether this differs between patients with and without homologous recombination deficiency (HRD), a DNA repair defect that increases sensitivity to platinum-based chemotherapy, remains open.
We address this using an ODE model of tumour-immune dynamics in HGSC, built around two cancer cell populations: immune-recognisable cells that drive T cell responses, and immune-invisible cells that accumulate through irreversible escape mutations. A sensitivity analysis shows that T cell proliferative capacity — not per-cell killing rate — determines whether immune control is maintained.
Adding platinum-based chemotherapy clears much of the tumour but leaves memory T cells relatively intact: through antigen-driven division, slower natural turnover, and lower chemotherapy sensitivity, memory cells outnumber effector T cells by over 600-fold at end of treatment. We then ask whether this memory reservoir delays relapse, and whether the effect differs in HRD-positive patients — providing a mechanistic rationale for memory T cell levels as a prognostic marker in HGSC.
