LILRB3 Supports Immunosuppressive Activity of Myeloid Cells and Tumor Development.

The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid tumors. Here, we report that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. LILRB3 blockade may prove to be a novel approach for immunotherapy of solid cancers.

MeHg production in eutrophic lakes: Focusing on the roles of algal organic matter and iron-sulfur-phosphorus dynamics.

The mechanisms by which eutrophication affects methylmercury (MeHg) production have not been comprehensively summarized, which hinders accurately predicting the MeHg risk in eutrophic lakes. In this review, we first discussed the effects of eutrophication on biogeochemical cycle of mercury (Hg). Special attentions were paid to the roles of algal organic matter (AOM) and iron (Fe)-sulfur (S)-phosphorus (P) dynamics in MeHg production. Finally, the suggestions for risk control of MeHg in eutrophic lakes were proposed. AOM can affect in situ Hg methylation by stimulating the abundance and activities of Hg methylating microorganisms and regulating Hg bioavailability, which are dependent on bacteria-strain and algae species, the molecular weight and composition of AOM as well as environmental conditions (e.g., light). Fe-S-P dynamics under eutrophication including sulfate reduction, FeS formation and P release could also play crucial but complicated roles in MeHg production, in which AOM may participate through influencing the dissolution and aggregation processes, structural order and surface properties of HgS nanoparticles (HgSNP). Future studies should pay more attention to the dynamics of AOM in responses to the changing environmental conditions (e.g., light penetration and redox fluctuations) and how such variations will subsequently affect MeHg production. The effects of Fe-S-P dynamics on MeHg production under eutrophication also deserve further investigations, especially the interactions between AOM and HgSNP. Remediation strategies with lower disturbance, greater stability and less cost like the technology of interfacial O2 nanobubbles are urgent to be explored. This review will deepen our understanding of the mechanisms of MeHg production in eutrophic lakes and provide theoretical guidance for its risk control.

Blocking LAIR1 signaling in immune cells inhibits tumor development.

The current immune checkpoint blockade therapy has been successful in treating some cancers but not others. New molecular targets and therapeutic approaches of cancer immunology need to be identified. Leukocyte associated immunoglobulin like receptor 1 (LAIR1) is an immune inhibitory receptor expressing on most immune cell types. However, it remains a question whether we can specifically and actively block LAIR1 signaling to activate immune responses for cancer treatment. Here we report the development of specific antagonistic anti-LAIR1 monoclonal antibodies and studied the effects of LAIR1 blockade on the anti-tumor immune functions. The anti-LAIR1 antagonistic antibody stimulated the activities of T cells, natural killer cells, macrophages, and dendritic cells in vitro. The single-cell RNA sequencing analysis of intratumoral immune cells in syngeneic human LAIR1 transgenic mice treated with control or anti-LAIR1 antagonist antibodies indicates that LAIR1 signaling blockade increased the numbers of CD4 memory T cells and inflammatory macrophages, but decreased those of pro-tumor macrophages, regulatory T cells, and plasmacytoid dendritic cells. Importantly, the LAIR1 blockade by the antagonistic antibody inhibited the activity of immunosuppressive myeloid cells and reactivated T cells from cancer patients in vitro and impeded tumor metastasis in a humanized mouse model. Blocking LAIR1 signaling in immune cells represents a promising strategy for development of anti-cancer immunotherapy.

The Effects of Transcutaneous Acupoint Electrical Stimulation on Cancer-related Fatigue and Negative Emotions in Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Transcutaneous electrical acupoint stimulation (TEAS) is a noninvasive and therapeutic technique that stimulated the acupoint by delivering electricity. Whether TEAS could relieve cancer-related fatigue (CRF), anxiety, and depression and improve the quality of life in cancer patients remains controversial. Thus, we conducted a thorough literature search of electronic Chinese and English databases for randomized controlled trials (RCTs) reporting the effect of CRF, anxiety, depression, and quality of life in cancer patients from inception to July 1st, 2021. The Cochrane Collaboration Risk of Bias criteria were used to assess the risk of bias for each included RCT. Continuous variables were analyzed using standardized mean difference (SMD) and 95% confidence interval (CI). A fixed-effects model was used for the meta-analysis of all outcomes. A total of nine RCTs with 924 cancer patients were included in this analysis, including 460 patients in the interventional group and 464 patients in the control group. We found that TEAS could significantly reduce CRF, depression, and anxiety (SWD = -0.83, 95% CI: -0.99 to -0.66, P < 0.05) and improve the quality of life (SWD = -1.37, 95% CI: -2.34 to -0.40, P < 0.05). The funnel plot analysis revealed no significant publication bias. We conclude that TEAS is beneficial for reducing CRF, depression, and anxiety and improving the quality of life of cancer patients, but additional high-quality evidence in the future is entailed to support this.

Leukocyte immunoglobulin-like receptor subfamily B: therapeutic targets in cancer.

Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1-5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs that recruit phosphatases to negatively regulate immune activation. The activation of LILRB signaling in immune cells may contribute to immune evasion. In addition, the expression and signaling of LILRBs in cancer cells especially in certain hematologic malignant cells directly support cancer development. Certain LILRBs thus have dual roles in cancer biology-as immune checkpoint molecules and tumor-supporting factors. Here, we review the expression, ligands, signaling, and functions of LILRBs, as well as therapeutic development targeting them. LILRBs may represent attractive targets for cancer treatment, and antagonizing LILRB signaling may prove to be effective anti-cancer strategies.

Significance of Vestibular Testing on Distinguishing the Nerve of Origin for Vestibular Schwannoma and Predicting the Preservation of Hearing.

BACKGROUND: Determining the nerve of origin for vestibular schwannoma (VS), as a method for predicting hearing prognosis, has not been systematically considered. The vestibular test can be used to investigate the function of the superior vestibular nerve (SVN) and the inferior vestibular nerve (IVN). This study aimed to preoperatively distinguish the nerve of origin for VS patients using the vestibular test, and determine if this correlated with hearing preservation. METHODS: A total of 106 patients with unilateral VS were enrolled in this study prospectively. Each patient received a caloric test, vestibular-evoked myogenic potential (VEMP) test, and cochlear nerve function test (hearing) before the operation and 1 week, 3, and 6 months, postoperatively. All patients underwent surgical removal of the VS using the suboccipital approach. During the operation, the nerve of tumor origin (SVN or IVN) was identified by the surgeon. Tumor size was measured by preoperative magnetic resonance imaging. RESULTS: The nerve of tumor origin could not be unequivocally identified in 38 patients (38/106, 35.80%). These patients were not subsequently evaluated. In 26 patients (nine females, seventeen males), tumors arose from the SVN and in 42 patients (18 females, 24 males), tumors arose from the IVN. Comparing with the nerve of origins (SVN and IVN) of tumors, the results of the caloric tests and VEMP tests were significantly different in tumors originating from the SVN and the IVN in our study. Hearing was preserved in 16 of 26 patients (61.54%) with SVN-originating tumors, whereas hearing was preserved in only seven of 42 patients (16.67%) with IVN-originating tumors. CONCLUSIONS: Our data suggest that caloric and VEMP tests might help to identify whether VS tumors originate from the SVN or IVN. These tests could also be used to evaluate the residual function of the nerves after surgery. Using this information, we might better predict the preservation of hearing for patients.