Maternal cancer during pregnancy and umbilical cord blood: evidence on immunobiology and translational implications for cellular therapy

Abstract Background Umbilical cord blood (UCB) is an established source of hematopoietic stem and progenitor cells (HSPCs) and immune-cell populations used in transplantation and investigated for cellular therapies. However, direct evidence regarding the biological characteristics of UCB obtained after pregnancies complicated by maternal cancer remains limited. Recent human research has provided new evidence concerning prenatal cancer treatment and neonatal hematopoietic cells, while related UCB studies provide context for immune-cell composition, maternal microchimerism, and cellular-therapy applications. Main body This narrative review distinguishes direct evidence from contextual evidence to assess the effects of maternal cancer and cancer treatment on UCB biology. A 2025 human study demonstrated increased mutational burden and treatment-related mutational signatures in neonatal cord-blood HSPCs following prenatal chemotherapy, whereas HSPCs from untreated pregnancies complicated by cancer were similar to those from healthy pregnancies. Other studies demonstrate that maternal cells can be detected in UCB and may be associated with differences in immune-cell composition. However, current evidence is insufficient to establish maternal-cancer-specific alterations in T cells, regulatory T cells, cytokine profiles, or natural killer-cell function. Studies of UCB-derived cellular therapies demonstrate the feasibility of T-cell, regulatory T-cell, and CAR-NK platforms but do not establish that maternal cancer or prenatal treatment alters their therapeutic performance. Conclusion Maternal cancer during pregnancy should not currently be considered an established cause of a defined immunological or functional UCB phenotype. The strongest direct evidence concerns prenatal chemotherapy-associated molecular changes in neonatal HSPCs. Other proposed effects remain insufficiently characterized. Prospective studies integrating maternal disease characteristics, treatment exposure, gestational timing, placental biology, UCB immune composition, molecular features, and neonatal follow-up are required before these findings can inform donor evaluation, cord-blood banking, or cellular-therapy practice.