Why Y matters? The implication of loss of Y chromosome in blood and cancer

Hematopoietic mosaic loss of Y chromosome (mLOY) has emerged as a potential male-specific accelerator of biological aging, increasing the risk of various age-related diseases, including cancer. Importantly, mLOY is not confined to hematopoietic cells; its presence has also been observed in nonhematological cancer cells, with the impact of this presence previously unknown. Recent studies have revealed that, whether occurring in leukocytes or cancer cells, mLOY plays a role in promoting the development of an immunosuppressive tumor microenvironment. This occurs through the modulation of tumor-infiltrating immune cells, ultimately enabling cancer cells to evade the vigilant immune system. In this review, we illuminate recent progress concerning the effects of hematopoietic mLOY and cancer mLOY on cancer progression. Examining cancer progression from the perspective of LOY adds a new layer to our understanding of cancer immunity, promising insights that hold the potential to identify innovative and potent immunotherapy targets for cancer. Hematopoietic mosaic loss of Y chromosome (mLOY) acts as a male-specific accelerator of biological aging and increases susceptibility to age-related diseases, including cancer. Recent findings indicate that hematopoietic mLOY, and its cancer cell counterpart, cancer LOY, promote an immunosuppressive tumor environment, helping cancer cells escape immune detection.image