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PNAS Papers Explore Diet-Gut Microbe Ties, Taxane Susceptible Breast Cancer, More

A team from Brown University, Princeton University, and the National Museums of Kenya looks at gut microbiome-diet relationships in almost three dozen large, East African herbivore species. The researchers relied on 16S ribosomal RNA gene sequencing and additional metabarcode marker sequencing to assess bacterial and plant representatives in fresh fecal samples collected from 27 native and half a dozen domesticated mammal species in a semi-arid savannah region in the Kenyan county Laikipia. Although diet, season, and species lifestyle seemed to affect the composition of herbivore gut microbiomes, the data suggested that a diverse diet did not usually correspond with microbial diversity in the gut. Overall, the authors say, the findings so far "reveal marked differences in the influence of environment on the degree of diet-microbiome covariation in free-ranging African megafauna, and this variation is not well explained by canonical predictors of nutritional ecology."

French researchers search for breast cancer features that boost susceptibility to neoadjuvant chemotherapy, focusing on 280 genes with known or suspected roles in microtubule regulation. Using expression data for almost 400 breast cancer cases profiled in the past, the team tracked down 17 microtubule-related genes with altered expression in tumors with pathological complete response to neoadjuvant chemotherapy, including a gene coding for the ATIP3 protein. With follow-up experiments in patient-derived xenograft models and breast cancer cell lines, the authors saw signs that lower-than-usual ATIP3 levels can enhance sensitivity to taxane chemotherapy such as paclitaxel. "Our results favor a mechanism by which the combination of ATIP3 deficiency and paclitaxel treatment induces excessive aneuploidy, which in turn results in elevated cell death," they report.

Investigators at the University of Pennsylvania and elsewhere outline results from a sequencing-based analysis aimed at characterizing within-tumor heterogeneity in metastatic melanoma cases, and its influence on T cell immune responses to such tumors. Using exome sequencing, transcriptome sequencing, and T cell receptor (TCR) analyses, the team looked for antigen-producing, single base mutations in multiple metastatic samples from the same patients, as well as the TCR clonotypes coinciding with them. Based on data from these and other analyses in melanoma patients with mutation-rich tumors, the authors report that "spontaneous antitumor CD8+ T cell immunity in peripheral blood and tumors was restricted to a few clonal neoantigens," hinting that "therapeutic vaccination is necessary as an adjunct to checkpoint inhibitor treatment."