Uncovering the Role of X Chromsome Inactivation Escapees in T Cell Function

forthcoming

Sex differences play a significant role in immune function, with women generally mounting stronger immune responses than men. A key factor behind these differences is the X chromosome, which contains many genes that are important for immune function. In females, who have two X chromosomes, one of the X chromosomes is usually inactivated in each cell to prevent an overdose of X-linked gene expression. This process is known as X-chromosome inactivation (XCI). However, some genes can escape this inactivation and are expressed from both X chromosomes. These “escapee” genes are often expressed at higher levels in females than in males, who only have one X chromosome. The X-CITE (X-Chromosome Inactivation and T cell Escape) project aims to elucidate the molecular mechanisms by which these XCI escapee genes influence T cell responses. Understanding these mechanisms is crucial, as T cells are central to the success of cancer immunotherapy, where sex-based differences in T cell function may impact treatment outcomes. By exploring the sex-biased expression of XCI escapee genes, this project will advance our understanding of sex differences in immune responses and provide new insights into how T cells can be manipulated to improve the efficacy of cancer immunotherapy. The research will be conducted at the Landsteiner Laboratory Amsterdam UMC-Sanquin (The Netherlands), under the supervision of Dr. Monika Wolkers, whose lab specializes in T cell biology and the enhancement of T cell functions in immunotherapy settings.