Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small-cell lung cancer

A partir de l'analyse du transcriptome de 232 080 cellules et l'analyse transcriptomique spatiale de tumeurs provenant de 19 patients atteints d'un cancer du poumon non à petites cellules, cette étude identifie des facteurs biologiques associés à la résistance des cellules cancéreuses à l'immunochimiothérapie

Résumé en anglais

Although immune checkpoint blockade (ICB) therapies have shifted the treatment paradigm for non-small-cell lung cancer (NSCLC), many patients remain resistant. Here we characterize the tumor cell states and spatial cellular compositions of the NSCLC tumor microenvironment (TME) by analyzing single-cell transcriptomes of 232,080 cells and spatially resolved transcriptomes of tumors from 19 patients before and after ICB–chemotherapy. We find that tumor cells and secreted phosphoprotein 1-positive macrophages interact with collagen type XI alpha 1 chain-positive cancer-associated fibroblasts to stimulate the deposition and entanglement of collagen fibers at tumor boundaries, obstructing T cell infiltration and leading to poor prognosis. We also reveal distinct states of tertiary lymphoid structures (TLSs) in the TME. Activated TLSs are associated with improved prognosis, whereas a hypoxic microenvironment appears to suppress TLS development and is associated with poor prognosis. Our study provides novel insights into different cellular and molecular components corresponding to NSCLC ICB–chemotherapeutic responsiveness, which will benefit future individualized immuno-chemotherapy.