T-cell expression of CXCL13 is associated with immunotherapy response in a sex-dependent manner in patients with lung cancer.

Emerging evidence in preclinical models demonstrates that antitumor immunity is not equivalent between males and females. However, more investigation in patients and across a wider range of cancer types is needed to fully understand sex as a variable in tumor immune responses. We investigated differences in T-cell responses between male and female patients with lung cancer by performing sex-based analysis of single cell transcriptomic datasets. We found that the transcript encoding CXC motif chemokine ligand 13 (CXCL13), which has recently been shown to correlate with T-cell tumor specificity, is expressed at greater levels in T cells isolated from female compared to male patients. Furthermore, increased expression of CXCL13 was associated with response to PD-1-targeting immunotherapy in female but not male patients. These findings suggest that there are sex-based differences in T-cell function required for response to anti-PD-1 therapy in lung cancer that may need to be considered during patient treatment decisions.

Chromosome-level Subgenome-aware de novo Assembly of Saccharomyces bayanus Provides Insight into Genome Divergence after Hybridization.

Interspecies hybridization is prevalent in various eukaryotic lineages and plays important roles in phenotypic diversification, adaption, and speciation. To better understand the changes that occurred in the different subgenomes of a hybrid species and how they facilitated adaptation, we completed chromosome-level de novo assemblies of all 16 pairs chromosomes for a recently formed hybrid yeast, Saccharomyces bayanus strain CBS380 (IFO11022), using Nanopore MinION long-read sequencing. Characterization of S. bayanus subgenomes and comparative analysis with the genomes of its parent species, S. uvarum and S. eubayanus, provide several new insights into understanding genome evolution after a relatively recent hybridization. For instance, multiple recombination events between the two subgenomes have been observed in each chromosome, followed by loss of heterozygosity (LOH) in most chromosomes in nine chromosome pairs. In addition to maintaining nearly all gene content and synteny from its parental genomes, S. bayanus has acquired many genes from other yeast species, primarily through the introgression of S. cerevisiae, such as those involved in the maltose metabolism. In addition, the patterns of recombination and LOH suggest an allotetraploid origin of S. bayanus. The gene acquisition and rapid LOH in the hybrid genome probably facilitated its adaption to maltose brewing environments and mitigated the maladaptive effect of hybridization.