Although cancer-associated fibroblasts (CAFs) are the most crucial stromal cells, characterizing their heterogeneity is far from complete. The authors report a novel subset of CAFs in oral squamous cell carcinoma (OSCC), which positively expressed CD68, the classic marker of macrophages. The spatial and temporal distribution of the CD68+ CAF subset of OSCC (n = 104) was determined by CD68/α-SMA immunohistochemistry of serial sections. The CD68+ α-SMA+ CAF subset was found to be elevated from dysplasia to OSCC. Moreover, although both the tumor center and invasive front harbor an abundant CD68+ CAF subset, patients with low-CD68+ CAFs in the tumor center showed more recurrence after operation and shorter survival time, indicating the different function of CD68+ CAFs in tumor initiation and progression.  https://www.selleckchem.com/products/wnt-c59-c59.html  Functional analysis in the OSCC-CAF co-culture system found knockdown of CD68 did not change the phenotype of CAFs, tumor growth, or migration. Unexpectedly, low-CD68+ CAFs were associated with aberrant immune balance. A high proportion of tumor-supportive Tregs was found in patients with low-CD68+ CAFs. Mechanistically, knockdown of CD68 in CAFs contributed to the up-regulation of chemokine CCL17 and CCL22 of tumor cells to enhance Treg recruitment. Thus, up-regulated CD68+ fibroblasts participate in tumor initiation, but the low-CD68+ CAF subset in OSCC is conducive to Treg recruitment in the tumor microenvironment and contribute to poor prognosis of OSCC patients. Tumor metastasis to the draining lymph nodes is an important indicator of patient prognosis and is tightly regulated by molecular interactions mediated by lymphatic endothelial cells (LECs). However, these mechanisms remain undefined in the head and neck squamous cell carcinomas (HNSCCs). HNSCC cells and LECs were used to determine the specific pathways mediating tumor-lymphatic cross talk. We investigated the effects of a pentacyclic triterpenoid, methyl 2-trifluoromethyl-3,11-dioxoolean-1,12-dien-30-oate (CF3DODA-Me), that is a potent anticancer agent on cancer-lymphatic interactions. In response to inflammation, LECs induced the CXCL9/10/11 chemokines with a concomitant increase in the CXCR3 receptor in tumor cells. CF3DODA-Me showed antiproliferative effects on tumor cells, altered cellular bioenergetics, and suppressed matrix metalloproteinases and chemokine receptors. It also suppressed the induction of CXCL11-CXCR3 axis and phosphatidylinositol 3-kinase/AKT pathways. Tumor cell migration to LECs was inhibited by blocking CXCL11 while recombinant CXCL11 significantly induced tumor migration, epithelial-to-mesenchymal transition, and matrix remodeling. Immunohistochemical analysis of HNSCC tumor arrays showed enhanced expression of CXCR3 and increased lymphatic vessel infiltration. Furthermore, The Cancer Genome Atlas RNA-sequencing data from HNSCC patients also showed a positive correlation between CXCR3 expression and lymphovascular invasion. Collectively, our data suggest a novel mechanism for cross talk between the LECs and HNSCC tumors through the CXCR3-CXCL11 axis and elucidate the role of the triterpenoid CF3DODA-Me in abrogating several of these tumor-promoting pathways. Liver regeneration is a fundamental biological process required for sustaining body homeostasis and restoring liver function after injury. Emerging evidence demonstrates that cytokines, growth factors, and multiple signaling pathways contribute to liver regeneration. Mammalian target of rapamycin complex 2 (mTORC2) regulates cell metabolism, proliferation and survival. The major substrates for mTORC2 are the AGC family members of kinases, including AKT, SGK, and PKC-α. We investigated the functional roles of mTORC2 during liver regeneration. Partial hepatectomy (PHx) was performed in liver-specific Rictor (the pivotal unit of mTORC2 complex) knockout (RictorLKO) and wild-type (Rictorfl/fl) mice. Rictor-deficient mice were found to be more intolerant to PHx and displayed higher mortality after PHx. Mechanistically, loss of Rictor resulted in decreased Akt phosphorylation, leading to a delay in hepatocyte proliferation and lipid droplets formation along liver regeneration. Overall, these results indicate an essential role of the mTORC2 signaling pathway during liver regeneration. The molecular mechanisms of prostate inflammation, a common disease of the prostate with symptoms of pain and/or heightened immune response, are still poorly understood. We hypothesized that heme oxygenase 1 (HO-1), an enzyme responsible for degradation of heme to carbon monoxide, bilirubin, and iron, is an important regulator of inflammation and epithelial responses in the prostate. Injection of nonuropathogenic Escherichia coli (MG1655 strain) or phosphate-buffered saline into the urethra of mice led to increased numbers of CD45+ leukocytes and mitotic markers (phosphorylated histone H3 and phosphorylated ERK1/2) in the prostate glands. Leukocyte infiltration was elevated in prostates harvested from mice that lacked HO-1 in the myeloid compartment. Conversely, exogenous carbon monoxide (250 ppm) increased IL-1β levels and suppressed cell proliferation in the prostates. Carbon monoxide did not affect the number of infiltrating CD45+ cells in the prostates of E. coli- or phosphate-buffered saline-treated mice. Interestingly, immunomodulatory effects of HO-1 and/or carbon monoxide correlated with early induction of the long-chain acyl-CoA synthetase 1 (ACSL1). ACSL1 was induced in response to E. coli infection in macrophages and was in part required for IL-1β expression and prostate cancer cell colony growth in soft agar. These results suggest that HO-1 and/or carbon monoxide might play a distinctive role in modulating prostate inflammation, cell proliferation, and IL-1β induction in part via an ACSL1-mediated pathway. Zika virus (ZIKV) is a reemerging human pathogen that causes congenital abnormalities, including microcephaly and eye disease. The cellular/molecular basis of ZIKV and host interactions inducing ocular and neuronal pathogenesis are unclear. Herein, we noted that the Hippo/Salvador-Warts-Hippo signaling pathway, which controls organ size through progenitor cell proliferation and differentiation, is dysregulated after ZIKV infection. In human fetal retinal pigment epithelial cells, there is an early induction of transcriptional coactivator, Yes-associated protein (YAP), which is later degraded with a corresponding activation of the TBK1-IRF3 type I interferon pathway. YAP/TAZ silencing results in reduced ZIKV replication, indicating a direct role of Hippo pathway in regulating ZIKV infection. Using an in vivo Ifnar1-/- knockout mouse model, ZIKV infection was found to reduce YAP/TAZ protein levels while increasing phosphorylated YAP Ser127 in the retina and brain. Hippo pathway is activated in major cellular components of the blood-brain barrier, including endothelial cells and astrocytes.