Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Lipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity.

Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna's Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity.

tRNA-derived small RNAs: their role in the mechanisms, biomarkers, and therapeutic strategies of colorectal cancer.

Colorectal cancer (CRC) is the third most prevalent malignancy and the second leading cause of cancer-related mortality worldwide, with an increasing shift towards younger age of onset. In recent years, there has been increasing recognition of the significance of tRNA-derived small RNAs (tsRNAs), encompassing tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Their involvement in regulating translation, gene expression, reverse transcription, and epigenetics has gradually come to light.

Engineered T cells secreting αB7-H3-αCD3 bispecific engagers for enhanced anti-tumor activity against B7-H3 positive multiple myeloma: a novel therapeutic approach.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy with increasing global incidence. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has shown efficacy in relapsed or refractory MM, but it faces resistance due to antigen loss and the tumor microenvironment. Bispecific T-cell engaging (BITE) antibodies also encounter clinical challenges, including short half-lives requiring continuous infusion and potential toxicities.

Characterizing tertiary lymphoid structures associated single-cell atlas in breast cancer patients.

The tertiary lymphoid structure (TLS) is recognized as a potential prognosis factor for breast cancer and is strongly associated with response to immunotherapy. Inducing TLS neogenesis can enhance the immunogenicity of tumors and improve the efficacy of immunotherapy. However, our understanding of TLS associated region at the single-cell level remains limited.

A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.

Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.

Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.

What are parents' preferences for Human Papillomavirus vaccination promotion messages and communication? Application of a discrete choice experiment to a French Caribbean setting.

Introduction: Human Papillomavirus (HPV) vaccine uptake in the French Caribbean has remained below 25% since introduction in 2007, which is well behind national and international targets. Using a discrete choice experiment (DCE), we explored parental preferences around HPV vaccination and optimized communication content in a sample of parents of middle-school pupils in Guadeloupe.

Methods: We conducted a cross-sectional survey in public and private middle age schools in Guadeloupe in June 2023 using an online questionnaire.

The systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatment.

Background: Metabolic pathways are known to significantly impact the development and advancement of lung cancer. This study sought to establish a signature related to butyrate metabolism that is specifically linked to lung adenocarcinoma (LUAD).

Methods: For the purpose of identifying butyrate metabolism-related differentially expressed genes (BMR-DEGs) in the TCGA-LUAD dataset, we introduced transcriptome data.

F-FAPI-42 PET/CT and F-FDG PET/CT in Patients with Malignant Digestive System Neoplasms: A Head-to-Head Comparative Study.

Purpose: Radionuclide-labeled fibroblast activation protein inhibitor (FAPI) is an emerging tumor tracer. We sought to assess the uptake and diagnostic performance of F-FAPI-42 PET/CT compared with simultaneous 2-deoxy-2[F]fluoro-D-glucose (F-FDG) PET/CT in primary and metastatic lesions in patients with malignant digestive system neoplasms and to determine the potential clinical benefit.

Procedures: Forty-two patients (men = 30, women = 12, mean age = 56.

Integrated bioinformatics and experimental analysis of CHAF1B as a novel biomarker and immunotherapy target in LUAD.

The prognosis and treatment efficacy of lung adenocarcinoma (LUAD), a disease with a high incidence, remains unsatisfactory. Identifying new biomarkers and therapeutic targets for LUAD is essential. Chromosomal assembly factor 1B (CHAF1B), a p60 component of the CAF-1 complex, is closely linked to tumor incidence and cell proliferation.

Integrating Practice-Changing Studies in Gynaecologic Oncology Through Clinical Illustrations.

Advances in gynaecologic oncology research lead to continuous updates in clinical guidelines. However, undergraduate medical education often lacks in-depth coverage of recent developments, limiting students' preparedness for evidence-based management of gynaecological cancers. This study aimed to bridge the educational gap by integrating case-based analyses of practice-changing studies into the undergraduate obstetrics and gynaecology course.

Survival After Orbital Exenteration for Primary Cutaneous Squamous Cell Carcinoma: A Retrospective Cohort Study.

Background: Locally advanced periorbital cutaneous squamous cell carcinoma (cSCC) may require orbital exenteration, which is highly morbid. As immunotherapy develops, orbit preservation may become widespread, and data benchmarking survival with current standard-of-care surgery and radiotherapy are essential to the integration of this emerging method into modern treatment paradigms. This study aimed to determine the survival of patients after orbital exenteration for cSCC and investigate contributing factors.

ETV7 limits the antiviral and antitumor efficacy of CD8 T cells by diverting their fate toward exhaustion.

Terminal exhaustion is a critical barrier to antitumor immunity. By integrating and analyzing single-cell RNA-sequencing and single-cell assay for transposase-accessible chromatin with sequencing data, we found that ETS variant 7 (ETV7) is indispensable for determining CD8 T cell fate in tumors. ETV7 introduction drives T cell differentiation from memory to terminal exhaustion, limiting antiviral and antitumor efficacy in male mice.

Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity.

Immune functions decline with aging, leading to increased susceptibility to various diseases including tumors. Exploring aging-related molecular targets in elderly patients with cancer is thus highly sought after. Here we find that an ER transmembrane enzyme, sterol O-acyltransferase 2 (SOAT2), is overexpressed in regulatory T (Treg) cells from elderly patients with lung squamous cell carcinoma (LSCC), while radiomics analysis of LSCC patients associates increased SOAT2 expression with reduced immune infiltration and poor prognosis.

CD93 blockade promotes effector T-cell infiltration and facilitates adoptive cell therapy in solid tumors.

Background: Adaptive cellular therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has been successful in the treatment of hemopoietic malignancies. However, poor trafficking of administered effector T cells to the tumor poses a great hurdle for this otherwise powerful therapeutic approach in solid cancers. Our previous study revealed that targeting CD93 normalizes tumor vascular functions to improve immune checkpoint blockade therapy.

Promotion of Triple Negative Breast Cancer Immunotherapy by Combining Bioactive Radicals with Immune Checkpoint Blockade.

Although immunotherapy has revolutionized clinical cancer treatment, the efficacy is limited due to the lack of tumor-associated antigens (TAAs) and the presence of compensatory immune checkpoints. To overcome the deficiency, a nano-system loaded with ozone and CD47 inhibitor RRx-001 is designed and synthesized. Upon irradiation, reactive oxygen species (ROS) generated from ozone reacts with nitric oxide (NO) metabolized from RRx-001 to form reactive nitrogen species (RNS), which presents a much stronger cell-killing ability than ROS.

GIMAP1 interacts with TMX1 to improve lung adenocarcinoma prognosis by influencing tumor immune microenvironment.

Recent studies have indicated that the GIMAP family is downregulated in lung cancer and correlates with poor prognosis, although the underlying mechanisms remain unclear. This study aimed to elucidate the mechanism behind GIMAP1 downregulation in lung cancer. Bioinformatics tools were employed to assess the correlation between the GIMAP family and various cancers.

Modulating the gut microbiota: A novel perspective in colorectal cancer treatment.

Colorectal cancer (CRC), the second leading cause of cancer-related deaths worldwide, is intricately linked to the dysregulation of the gut microbiota. Manipulating the gut microbiota has emerged as a novel strategy for the prevention and treatment of CRC. Natural products, a pivotal source in new drug discovery, have shown promise in recent research as regulators of the gut microbiota, offering potential applications in the prevention and treatment of CRC.

Ultrasound-triggered drug-loaded nanobubbles for enhanced T cell recruitment in cancer chemoimmunotherapy.

Chemotherapy combined with immunotherapy is a highly promising approach for treating tumors. However, chemotherapeutic drugs often fail to accumulate effectively at the tumor site after systemic administration and they lack sufficient immunogenicity to activate adaptive immunity, making an effective T-cell immune response within the tumor microenvironment difficult to achieve. Here, this work developed drug-loaded nanobubbles (DTX-R837@NBs) that encapsulate the chemotherapy drug docetaxel and the immune adjuvant R837 via a thin-film hydration method.

MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy.

Background: Breast cancer had been the most frequently diagnosed cancer among women, making up nearly one-third of all female cancers. Hormone receptor-positive breast cancer (HR+BC) was the most prevalent subtype of breast cancer and exhibited significant heterogeneity. Despite advancements in endocrine therapies, patients with advanced HR+BC often faced poor outcomes due to the development of resistance to treatment.

Comparative evaluation of PD-L1 expression and tumor immune microenvironment in molecular subtypes of muscle-invasive bladder cancer and its correlation with survival outcomes.

Objectives: Immune checkpoint inhibitors have revolutionized treatment of platinum-refractory advanced bladder cancer, offering hope where options are limited. Response varies, however, influenced by factors such as the tumor's immune microenvironment and prior therapy. Muscle-invasive bladder cancer (MIBC) is stratified into molecular subtypes, with distinct clinicopathologic features affecting prognosis and treatment.

Chimeric Antigen Receptor-T Cells in Colorectal Cancer: Pioneering New Avenues in Solid Tumor Immunotherapy.

Colorectal cancer (CRC) remains a major global health burden, being one of the most prevalent cancers with high mortality rates. Despite advances in conventional treatment modalities, patients with metastatic CRC often face limited options and poor outcomes. Chimeric antigen receptor-T (CAR-T) cell therapy, initially successful in hematologic malignancies, presents a promising avenue for treating solid tumors, including CRC.

Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy.

Brain metastasis (BM) is a poor prognostic factor in cancer patients. Despite showing efficacy in many extracranial tumors, immunotherapy with anti-PD-1 monoclonal antibody (mAb) or anti-CTLA-4 mAb appears to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti-PD-1 and anti-CTLA-4 mAbs has a potent antitumor effect on BM, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies.

An Albumin-Photosensitizer Supramolecular Assembly with Type I ROS-Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy.

Photodynamic therapy holds great potentials in cancer treatment, yet its effectiveness in hypoxic solid tumor is limited by the oxygen-dependence and insufficient oxidative potential of conventional type II reactive oxygen species (ROS). Herein, the study reports a supramolecular photosensitizer, BSA@TPE-BT-SCT NPs, through encapsulating aggregation-enhanced emission photosensitizer by bovine serum albumin (BSA) to significantly enhance ROS, particularly less oxygen-dependent type I ROS for photodynamic immunotherapy. The abundant type I ROS generated by BSA@TPE-BT-SCT NPs induce multiple forms of programmed cell death, including apoptosis, pyroptosis, and ferroptosis.