This article from Nature Genetics presents a multi-omic study using single-cell and spatial transcriptomics to understand resistance to immuno-chemotherapy in non-small-cell lung cancer (NSCLC). Researchers analyzed tumor samples from patients before and after treatment to identify cellular and molecular factors associated with poor outcomes. A key finding reveals that collagen type XI alpha 1 chain-positive (COL11A1+) cancer-associated fibroblasts (CAFs) and secreted phosphoprotein 1-positive (SPP1+) macrophages accumulate at tumor boundaries, forming a structure that physically blocks T cell infiltration. Additionally, the study characterizes different maturation states of tertiary lymphoid structures (TLSs), noting that activated TLSs are linked to improved prognosis, while a hypoxic microenvironment appears to suppress their beneficial development in non-responders. Overall, the research suggests several potential biomarkers and therapeutic targets aimed at overcoming treatment resistance by modulating the tumor microenvironment.
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