Acquired resistance to immunotherapy by physical barriers with cancer cell-expressing collagens in non-small cell lung cancer.

ABSTRACT: Immunotherapy has become the standard treatment for many types of cancers, but an increasing number of patients who initially respond to these treatments develop acquired immunotherapy resistance (AIR). Here, we recapitulated the entire process of immunotherapy from response to AIR in mice with non-small cell lung cancer (NSCLC). With implanted tumor organoids derived from these models and serial transplants, we demonstrated that tumor cell-intrinsic mechanisms contributed significantly to AIR. Single-cell RNA sequencing and electron microscope assays revealed that resistant tumor cell-expressing collagens, including Col3a1 and Col6a1, formed multiple physical barriers surrounding tumor cells. Disruption of these barriers by collagenase or knockout of both Col3a1 and <

SUBMITTER: Wang M 

PROVIDER: S-EPMC12184647 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature