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.

References:

• Yan Y, Sun D, Hu J, et al. Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small-cell lung cancer[J]. Nature Genetics, 2025, 57(1): 126-139.