LILRB3 Modulates Acute Myeloid Leukemia Progression and Acts as an Effective Target for CAR T-cell Therapy.

Identifying novel cell surface receptors that regulate leukemia cell differentiation and can be targeted to inhibit cellular proliferation is crucial to improve current treatment modalities in acute myeloid leukemia (AML), especially for relapsed or chemotherapy-refractory leukemia. Leukocyte immunoglobulin-like receptor type B (LILRB) is an immunomodulatory receptor originally found to be expressed in myeloid cells. In this study, we found that LILRB receptors can be induced under inflammatory stimuli and chemotherapy treatment conditions. Blockade of LILRB3 inhibited leukemia cell proliferation and leukemia progression. In addition, treatment with LILRB3 blocking antibodies upregulated myeloid lineage differentiation transcription factors, including PU.1, C/EBP family, and IRF, whereas phosphorylation of proliferation regulators, for example, AKT, cyclin D1, and retinoblastoma protein, was decreased. Conversely, transcriptomic analysis showed LILRB3 activation by agonist antibodies may enhance leukemia survival through upregulation of cholesterol metabolism, which has been shown to promote leukemia cell survival. Moreover, LILRB3-targeted CAR T cells exhibited potent antitumor effects both in vitro and in vivo. Taken together, our results suggest that LILRB3 is a potentially potent target for multiple treatment modalities in AML. SIGNIFICANCE: LILRB3 regulates differentiation and proliferation in acute myeloid leukemia and can be targeted with monoclonal antibodies and CAR T cells to suppress leukemia growth.

Complications associated with L4-5 anterior retroperitoneal trans-psoas interbody fusion: a single institution series.

BACKGROUND: Lateral lumbar interbody fusion (LLIF), first described in the literature in 2006 by Ozgur et al., involves direct access to the lateral disc space via a retroperitoneal trans-psoas tubular approach. Neuromonitoring is vital during this approach since the surgical corridor traverses the psoas muscle where the lumbar plexus lies, risking injury to the lumbosacral plexus that could result in sensory or motor deficits. The risk of neurologic injury is especially higher at L4-5 due to the anatomy of the plexus at this level. Here we report our single-center clinical experience with L4-5 LLIF. METHODS: A retrospective chart review of all patients who underwent an L4-5 LLIF between May 2016 and March 2019 was performed. Baseline demographics and clinical characteristics, such as body mass index (BMI), medical comorbidities, surgical history, tobacco status, operative time and blood loss, length of stay (LOS), and post-op complications were recorded. RESULTS: A total of 220 (58% female and 42% male) cases were reviewed. The most common presenting pathology was spondylolisthesis. The average age, BMI, operative time, blood loss, and LOS were 64.6 years, 29 kg/m2, 214 min, 75 cc, and 2.5 days respectively. A review of post-operative neurologic deficits revealed 31.4% transient hip flexor weakness and 4.5% quadricep weakness on the approach side. At 3-week follow-up, 9.1% of patients experienced mild hip flexor weakness (4 or 4+/5), 0.9% reported mild quadricep weakness, and 9.5% reported anterior thigh dysesthesias; 93.2% of patients were discharged home and 2.3% were readmitted within the first 30 days post discharge. Female sex, higher BMI and longer operative time were associated with hip flexor weakness. CONCLUSIONS: LLIF at L4-5 is a safe, feasible, and versatile approach to the lumbar spine with an acceptable approach-related sensory and motor neurologic complication rates.

Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment.

Tumor-mediated regulation of the host immune system involves an intricate signaling network that results in the tumor's inherent survival benefit. Myeloid cells are central in orchestrating the mechanisms by which tumors escape immune detection and continue their proliferative programming. Myeloid cell activation has historically been classified using a dichotomous system of classical (M1-like) and alternative (M2-like) states, defining general pro- and anti-inflammatory functions, respectively. Explosions in bioinformatics analyses have rapidly expanded the definitions of myeloid cell pro- and anti-inflammatory states with different combinations of tissue- and disease-specific phenotypic and functional markers. These new definitions have allowed researchers to target specific subsets of disease-propagating myeloid cells in order to modify or arrest the natural progression of the associated disease, especially in the context of tumor-immune interactions. Here, we discuss the myeloid cell contribution to solid tumor initiation and maintenance, and strategies to reprogram their phenotypic and functional fate, thereby disabling the network that benefits tumor survival.

Corrigendum: Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment.

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