Cancer‐associated fibroblasts in nonsmall cell lung cancer: From molecular mechanisms to clinical implications

Abstract

Lung cancer is the common and leading cause of cancer death worldwide. The tumor microenvironment has been recognized to be instrumental in tumorigenesis. To have a deep understanding of the molecular mechanism of nonsmall cell lung carcinoma (NSCLC), cancer-associated fibroblasts (CAFs) have gained increasing research interests.CAFs belong to the crucial and dominant cell population in the tumor microenvironment to support the cancer cells. The interplay and partnership between cancer cells and CAFs contribute to each stage of tumorigenesis. CAFs exhibit prominent heterogeneity and secrete different kinds of cytokines and chemokines, growth factors and extracellular matrix proteins involved in cancer cell proliferation, invasion, metastasis and chemoresistance. Many studies focused on the protumorigenic functions of CAFs, yet many challenges about the heterogeneity of CAFS remain unresolved. This review comprehensively summarized the tumor-promoting role and molecular mechanisms of CAFs in NSCLC, including their origin, phenotypic changes and heterogeneity and their functional roles in carcinogenesis. Meanwhile, we also highlighted the updated molecular classifications based on the molecular features and functional roles of CAFs.

Paracrine Regulation and Immune System Pathways in the Inflammatory Tumor Microenvironment of Lung Cancer: Insights into Oncogenesis and Immunotherapeutic Strategies

“…Cancer-associated fibroblasts (CAFs), critical components of the stromal compartment in the TME, actively participate in paracrine regulation [ 8 , 9 , 10 ]. CAFs are known to secrete growth factors like fibroblast growth factor (FGF) and transforming growth factor-beta (TGF-β), which can stimulate cancer cell proliferation, epithelial–mesenchymal transition (EMT), and invasiveness [ 8 , 9 , 10 , 11 ].…”

“…Cancer-associated fibroblasts (CAFs), critical components of the stromal compartment in the TME, actively participate in paracrine regulation [ 8 , 9 , 10 ]. CAFs are known to secrete growth factors like fibroblast growth factor (FGF) and transforming growth factor-beta (TGF-β), which can stimulate cancer cell proliferation, epithelial–mesenchymal transition (EMT), and invasiveness [ 8 , 9 , 10 , 11 ]. Moreover, C-X-C-type chemokines including CXCL8 (IL-8), CXCL2, and CXCL12 secreted by CAFs are also involved in tumor proliferation by promoting angiogenesis and metastasis (CXCL8 & CXCL12) and increasing PD-L1 expression (CXCL2) [ 9 , 12 , 13 , 14 ].…”

Cell Proteomic Footprinting: Advances in the Quality of Cellular and Cell-Derived Cancer Vaccines

“…In addition human cancer cells, endothelial cells (human microvascular endothelial cells, HMECs), and fibroblasts of various origins are represented. These cell types, like cancer cells themselves, are also considered targets for immunotherapy, as they are part of the tumor microenvironment and are required to ensure its functioning [ 75 , 76 , 77 , 78 , 79 ].…”

Interpretable spatially aware dimension reduction of spatial transcriptomics with STAMP

“…The analysis revealed upregulated cytokine signaling, which can be attributed to inflammatory molecules secreted within the tumor tissue 42 . Fibrosis pathways were also upregulated, suggesting a potential overlap in molecular mechanisms between the CAFs and the development of pulmonary fibrosis pathways 43,44 . Finally, the wound healing pathway showed upregulation, which suggested their activation and differentiation to become myofibroblasts.…”