Public conference as part of a search committee in Pathology.

Summary: Hematopoietic stem cells (HSCs) lose regenerative capacity and shift toward myeloid-biased differentiation with age, leading to reduced lymphoid populations and immune dysfunction. This decline, linked to accumulation of damaged mitochondria, increases susceptibility to severe infections and the onset of cancer in older adults. We found that targeting mitochondrial recycling and metabolism can reverse HSCs myeloid bias, thus preserving lymphoid populations and immune function.
Later, we showed that CAR-T cells generated from aged mice and older patients are unable to maintain an appropriate stem-like phenotype and control tumor growth. Importantly, the re-establishment of mitochondrial function restores CAR-T cell anti tumor response. Overall, restoring mitochondrial fitness in aged HSCs and immune cells enhances hematopoietic and immune function and improve cancer immunotherapy efficacy.