Multiple influence of immune cells in the bone metastatic cancer microenvironment on tumors.

Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis.

ZIF-8-Encapsulated Pexidartinib Delivery via Targeted Peptide-Modified M1 Macrophages Attenuates MDSC-Mediated Immunosuppression in Osteosarcoma.

Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages.

Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity.

Bone is one of the most common sites of tumor metastases. During the last step of bone metastasis, cancer cells colonize and disrupt the bone matrix, which is maintained mainly by osteocytes, the most abundant cells in the bone microenvironment. However, the role of osteocytes in bone metastasis is still unclear.

Cancer cells reprogram to metastatic state through the acquisition of platelet mitochondria.

Metastasis is the major cause of cancer deaths, and cancer cells evolve to adapt to various tumor microenvironments, which hinders the treatment of tumor metastasis. Platelets play critical roles in tumor development, especially during metastasis. Here, we elucidate the role of platelet mitochondria in tumor metastasis.

An On-Demand Collaborative Innate-Adaptive Immune Response to Infection Treatment.

Deep tissue infection is a common clinical issue and therapeutic difficulty caused by the disruption of the host antibacterial immune function, resulting in treatment failure and infection relapse. Intracellular pathogens are refractory to elimination and can manipulate host cell biology even after appropriate treatment, resulting in a locoregional immunosuppressive state that leads to an inadequate response to conventional anti-infective therapies. Here, a novel antibacterial strategy involving autogenous immunity using a biomimetic nanoparticle (NP)-based regulating system is reported to induce in situ collaborative innate-adaptive immune responses.

PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner.

Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) pathway is conventionally considered as an important pathway to promote osteogenesis; however, recent study suggested its role during osteogenesis to be controversial. Regarding the differential functions of this pathway during 3 stages of bone healing, we hypothesized that temporal inhibition of PDGF-BB/PDGFR-β pathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells, toward osteogenic lineage, which leads to improved bone regeneration. We first validated that inhibition of PDGFR-β at late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.

Human γδ T cells induce CD8 T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK.

Human Vγ9Vδ2 T cells have attracted considerable attention as novel alternative antigen-presenting cells (APCs) with the potential to replace dendritic cells in antitumor immunotherapy owing to their high proliferative capacity and low cost. However, the utility of γδ T cells as APCs to induce CD8 T cell-mediated antitumor immune response, as well as the mechanism by which they perform APC functions, remains unexplored. In this study, we found that activated Vγ9Vδ2 T cells were capable of inducing robust CD8 T cell responses in osteosarcoma cells.

Enhancement of T cell infiltration tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors.

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy (ACT) against solid tumors. Here, we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors. Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8 T cells, which led to improved antitumor outcomes.

Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion.

Chemotherapy elicits tumor immune evasion with poorly characterized mechanisms. Here, we demonstrate that chemotherapy markedly enhances the expression levels of CD47 in osteosarcoma tissues, which are positively associated with patient mortality. We reveal that macrophages in response to chemotherapy secrete interleukin-18, which in turn upregulates expression of L-amino acid transporter 2 (LAT2) in tumor cells for substantially enhanced uptakes of leucine and glutamine, two potent stimulators of mTORC1.

C-myc/TSPEAR-AS2 Axis Facilitates Breast Cancer Growth and Metastasis in a GLUT1-Dependent Glycolysis Manner.

A large number of facts have shown that epigenetic modification and metabolic reprogramming represented by noncoding RNA play an important role in the invasion and metastasis of breast cancer, but the mechanism is not clear. The purpose of our study is to find a new biomarker of breast cancer and to provide a new perspective for regulating glucose metabolism and aerobic glycolysis of BC. In this paper, by downregulating C-myc protein, our team found that the expression of long-chain noncoding RNATSPAR-AS2 was significantly downregulated.

Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value.

Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations.

Clinical Features and Serological Markers Risk Model Predicts Overall Survival in Patients Undergoing Breast Cancer and Bone Metastasis Surgeries.

Background: Surgical therapy of breast cancer and bone metastasis can effectively improve the prognosis of breast cancer. However, after the first operation, the relationship between preoperative indicators and outcomes in patients who underwent metastatic bone surgery remained to be studied. Purpose 1.