Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancerJingjing Qi, Hongxiang Sun, Yao Zhang et al.|Nature Communications|2022 Abstract Colorectal cancer (CRC) is among the most common malignancies with limited treatments other than surgery. The tumor microenvironment (TME) profiling enables the discovery of potential therapeutic targets. Here, we profile 54,103 cells from tumor and adjacent tissues to characterize cellular composition and elucidate the potential origin and regulation of tumor-enriched cell types in CRC. We demonstrate that the tumor-specific FAP + fibroblasts and SPP1 + macrophages were positively correlated in 14 independent CRC cohorts containing 2550 samples and validate their close localization by immuno-fluorescent staining and spatial transcriptomics. This interaction might be regulated by chemerin, TGF-β, and interleukin-1, which would stimulate the formation of immune-excluded desmoplasic structure and limit the T cell infiltration. Furthermore, we find patients with high FAP or SPP1 expression achieved less therapeutic benefit from an anti-PD-L1 therapy cohort. Our results provide a potential therapeutic strategy by disrupting FAP + fibroblasts and SPP1 + macrophages interaction to improve immunotherapy.
Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathwayMaolan Li, Zhou Zhang, Xiaoguang Li et al.|Nature Genetics|2014 Deterministic reprogramming of neutrophils within tumorsNeutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1 + state. Reprogrammed dcTRAIL-R1 + neutrophils predominantly localize to a glycolytic and hypoxic niche at the tumor core and exert pro-angiogenic function that favors tumor growth. We found similar trajectories in neutrophils across multiple tumor types and in humans, suggesting that targeting this program may provide a means of enhancing certain cancer immunotherapies.
Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic CancerYi-Ping Wang, Wei Zhou, Jian Wang et al.|Molecular Cell|2016 MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathwayXiangsong Wu, Xu-An Wang, Wenguang Wu et al.|Cancer Biology & Therapy|2014 Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies have demonstrated that MALAT1 plays an important role in other malignancies. However, little is known about the role of MALAT1 in gallbladder carcinoma (GBC), which is the most common cancer of the biliary tract and has an extremely poor prognosis. In this study, we focused on the expression, biological functions and mechanism of MALAT1 in GBC and found that MALAT1 was significantly upregulated in GBC tissues compared with corresponding non-cancerous tissues. Knockdown of MALAT1 in GBC cell lines using lentivirus-mediated RNA interference significantly inhibited the proliferation and metastasis of the GBC cells both in vitro and in vivo. Furthermore, ERK/MAPK pathway was found to be inactivated in the GBC cell lines after MALAT1 knockdown. These results indicated that MALAT1 might serve as an oncogenic lncRNA that promotes proliferation and metastasis of GBC and activates the ERK/MAPK pathway