LAMTOR1 Phosphorylation of Exo70 Facilitates Tumor-Associated Macrophage Polarization to Restrain CD8+ T Cell Function in HCC

The tumor microenvironment controls the progression of tissue homeostasis leading to cancer.Accumulation of anti-inflammatory tumor-associated macrophages (TAM) has also been linked to worsening clinical outcomes as well as resistance to treatment in hepatocellular carcinoma(HCC).The current immune landscape for regulation by the presence of TAMs has been studies.It is known that LAMTOR1 undergoes phosphorylation to bind to Exo70 and other exocyst components and is enhancing the secretion of TGFB1 to facilitate the polarization of TAMs.The tumor-conditioned macrophages(TCM) numbers also correlated with enhanced number of regulatory T cells(Tregs) and decreased CD8+T cells in HCC.Mechanistically,TCM enhanced IL-10 production to diminished CD8+T cell activities.Our data demonstrate a novel immune therapeutic approach targeting TAMs immune suppression of T cell anti-tumor activities.

Emerging Nanoparticle Strategies for Modulating Tumor-Associated Macrophage Polarization

Immunotherapy has made great progress in recent years, yet the efficacy of solid tumors remains far less than expected. One of the main hurdles is to overcome the immune-suppressive tumor microenvironment (TME). Among all cells in TME, tumor-associated macrophages (TAMs) play pivotal roles because of their abundance, multifaceted interactions to adaptive and host immune systems, as well as their context-dependent plasticity. Underlying the highly plastic characteristic, lots of research interests are focused on repolarizing TAMs from M2-like pro-tumor phenotype towards M1-like antitumoral ones. Nanotechnology offers great opportunities for targeting and modulating TAM polarization to mount the therapeutic efficacy in cancer immunotherapy. Here, this mini-review highlights those emerging nano-approaches for TAM repolarization in the last three years.

Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages

Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2+ TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44+ TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy.

OLFML2B Is a Robust Prognostic Biomarker in Bladder Cancer Through Genome-Wide Screening: A Study Based on Seven Cohorts

BackgroundBladder cancer lacks useful and robust prognostic markers to stratify patients at risk. Our study is to identify a robust prognostic marker for bladder cancer.MethodsThe transcriptome and clinical data of bladder cancer were downloaded from multiple databases. We searched for genes with robust prognosis by Kaplan-Meier analysis of the whole genome. CIBERSORT and TIMER algorithm was used to calculate the degree of immune cell infiltration.ResultsWe identified OLFML2B as a robust prognostic marker for bladder cancer in five cohorts. Kaplan-Meier analysis showed that patients with a high level of OLFML2B expression had a poor prognosis. The expression of OLFML2B increased with the increase of stage and grade. We found that patients with high expression of OLFML2B still had a poor prognosis in two small bladder cancer cohorts. OLFML2B also has the prognostic ability in ten other tumors, and the prognosis is poor in high expression. The correlation analysis between OLFML2B and immune cells showed that it was positively correlated with the degree of macrophage infiltration and highly co-expressed with tumor-associated macrophage markers. Finally, the Wound-healing assay and Colony formation assay results showed that the migration and proliferation ability of bladder cancer cell lines decreased after the knockdown of OLFML2B.ConclusionsIn summary, OLFML2B is a robust risk prognostic marker, and it can help patients with bladder cancer improve individualized treatment.