Cancer-associated fibroblasts and the tumor microenvironment in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) has a markedly poor prognosis as it progresses, and the prognosis is still unsatisfactory even with modern treatments. Cancer is composed of not only cancer cells, but also stroma consisting of various cell types. Cancer-associated fibroblasts (CAFs) are a major component of the stroma and the associated tumor microenvironment (TME). Particularly, CAFs are a critical component in elucidating the biological mechanisms of cancer progression and new therapeutic targets. This article outlines the TME formed by CAFs in NSCLC.Focusing on the TME in NSCLC, we discuss the mechanisms by which CAFs are involved in cancer progression, drug resistance, and the development of therapies targeting CAFs.In the TME, CAFs profoundly contribute to tumor progression by interacting with cancer cells through direct contact or paracrine cytokine signaling. CAFs also interact with various other stromal components to establish a tumor-promoting immunosuppressive microenvironment and remodel the extracellular matrix. Furthermore, these effects are closely associated with drug resistance. Further elucidation of the stromal microenvironment, including CAFs, could prove to be crucial in the treatment of NSCLC.