Dissecting the Tumor-Immune Landscape in Chimeric Antigen Receptor T-cell Therapy: Key Challenges and Opportunities for a Systems Immunology Approach.

The adoptive transfer of genetically engineered chimeric antigen receptor (CAR) T cells has opened a new frontier in cancer therapy. Unlike the paradigm of targeted therapies, the efficacy of CAR T-cell therapy depends not only on the choice of target but also on a complex interplay of tumor, immune, and stromal cell communication. This presents both challenges and opportunities from a discovery standpoint.

Myeloid Cell Hypoxia-Inducible Factors Promote Resolution of Inflammation in Experimental Colitis.

Colonic tissues in Inflammatory Bowel Disease (IBD) patients exhibit oxygen deprivation and activation of hypoxia-inducible factor 1α and 2α (HIF-1α and HIF-2α), which mediate cellular adaptation to hypoxic stress. Notably, macrophages and neutrophils accumulate preferentially in hypoxic regions of the inflamed colon, suggesting that myeloid cell functions in colitis are HIF-dependent. By depleting ARNT (the obligate heterodimeric binding partner for both HIFα subunits) in a murine model, we demonstrate here that myeloid HIF signaling promotes the resolution of acute colitis.

Triglycerides Promote Lipid Homeostasis during Hypoxic Stress by Balancing Fatty Acid Saturation.

Lipid droplets, which store triglycerides and cholesterol esters, are a prominent feature of clear cell renal cell carcinoma (ccRCC). Although their presence in ccRCC is critical for sustained tumorigenesis, their contribution to lipid homeostasis and tumor cell viability is incompletely understood. Here we show that disrupting triglyceride synthesis compromises the growth of both ccRCC tumors and ccRCC cells exposed to tumor-like conditions.

Genetic diversity in Svaneti and its implications for the human settlement of the Highland Caucasus.

Objectives: In this study, we characterized genetic diversity in the Svans from northwestern Georgia to better understand the phylogeography of their genetic lineages, determine whether genetic diversity in the highland South Caucasus has been shaped by language or geography, and assess whether Svan genetic diversity was structured by regional residence patterns.

Materials And Methods: We analyzed mtDNA and Y-chromosome variation in 184 individuals from 13 village districts and townlets located throughout the region. For all individuals, we analyzed mtDNA diversity through control region sequencing, and, for males, we analyzed Y-chromosome diversity through SNP and STR genotyping.