Predictive value of CCL2 in the prognosis and immunotherapy response of glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor with a poor prognosis. The C-C motif chemokine ligand 2 (CCL2) has shown abnormal expression associated with progression of multiple malignancies, however, its role in predicting the prognosis and immunotherapy response of GBM remains poorly understood. RESULTS: CCL2 was highly expressed in GBM as analyzed by integrating CGGA, GEPIA and UALCAN online platforms, and further verified by histologic examinations, qRT-PCR analysis, and independent GEO datasets. CCL2 could serve as an independent prognostic factor for both the poor overall survival and progression-free survival of GBM patients based on TCGA data, univariate and multivariate cox analyses. Functional enrichment analysis revealed that CCL2 mainly participated in the regulation of chemokine signaling pathway and inflammatory response. Further, CCL2 expression was positively correlated with CD4 T cells, macrophages, neutrophils and myeloid dendritic cells infiltrating GBM as calculated by the TIMER2.0 algorithm. Importantly, the tumor immune dysfunction and exclusion (TIDE) algorithm showed that in CCL2-high GBM group, the expression of CD274, CTLA4, HAVCR2 and other immune checkpoints were significantly increased, and the immune checkpoint blockade (ICB) therapy was accordingly more responsive. CONCLUSIONS: CCL2 can be used as a predictor of prognosis as well as immunotherapy response in GBM, offering potential clinical implications.

The Versatile Roles of Cancer-Associated Fibroblasts in Colorectal Cancer and Therapeutic Implications.

The tumor microenvironment (TME) is populated by abundant cancer-associated fibroblasts (CAFs) that radically influence the disease progression across many cancers, including the colorectal cancer (CRC). In theory, targeting CAFs holds great potential in optimizing CRC treatment. However, attempts to translate the therapeutic benefit of CAFs into clinic practice face many obstacles, largely due to our limited understanding of the heterogeneity in their origins, functions, and mechanisms. In recent years, accumulating evidence has uncovered some cellular precursors and molecular markers of CAFs and also revealed their versatility in impacting various hallmarks of CRC, together helping us to better define the population of CAFs and also paving the way toward their future therapeutic targeting for CRC treatment. In this review, we outline the emerging concept of CAFs in CRC, with an emphasis on their origins, biomarkers, prognostic significance, as well as their functional roles and underlying mechanisms in CRC biology. At last, we discuss the prospect of harnessing CAFs as promising therapeutic targets for the treatment of patients with CRC.