Mitochondrial respiratory complex III sustains IL-10 production in activated macrophages and promotes tumor-mediated immune evasion.

The cytokine interleukin-10 (IL-10) limits the immune response and promotes resolution of acute inflammation. Because of its immunosuppressive effects, IL-10 up-regulation is a common feature of tumor progression and metastasis. Recently, IL-10 regulation has been shown to depend on mitochondria and redox-sensitive signals.

Triple knockdown of , , and in T cells reduces CAR-T cell toxicity but preserves activity against solid tumors in mice.

Chimeric antigen receptor (CAR)-T cell therapies have revolutionized the landscape of cancer treatment, in particular in the context of hematologic malignancies. However, for solid tumors that lack tumor-specific antigens, CAR-T cells can infiltrate and attack nonmalignant tissues expressing the CAR target antigen, leading to on-target, off-tumor toxicity. Severe on-target, off-tumor toxicities have been observed in clinical trials of CAR-T therapy for solid tumors, highlighting the need to address this issue.

Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and the second leading cause of cancer-related mortality globally. Despite advancements in current HCC treatment, it remains a malignancy with poor prognosis. Therefore, developing novel treatment options for patients with HCC is urgently needed.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

[The impact of innate immune response on the efficacy of oncolytic viruses].

Oncolytic viruses represent a promising class of immunotherapeutic agents for the treatment of malignant tumors. The proposed mechanism of action of various oncolytic viruses has initially been explained by the ability of such viruses to selectively lyse tumor cells without damaging healthy ones. Recently, there have emerged more studies determining the effect of the antiviral immunostimulating mechanisms on the effectiveness of treatment in cancer patients.

Enhanced antitumor efficacy of nanostructured lipid carrier co-loaded with docetaxel and 5-fluorouracil for targeted gastric cancer therapy.

This study presents nanostructured lipid carrier (NLC) co-loaded with Docetaxel (DCT) and 5-Fluorouracil (5-FU) as a targeted therapeutic approach for gastric cancer (GC). Using nanoprecipitation, NLC-DCT/5-FU were synthesized and exhibited an average particle size of 215.3 ± 10.

Suppression of chemically induced mammary cancer by early-life oral administration of cholera toxin in mice is associated with aberrant regulation of Bmp and Notch signaling pathways.

Background: Lately, significant attention has been drawn towards the potential efficacy of cholera toxin (CT)-an exotoxin produced by the small intestine pathogenic bacterium Vibrio cholera-in modulating cancer-promoting events. In a recent study, we demonstrated that early-life oral administration of non-pathogenic doses of CT in mice suppressed chemically-induced carcinogenesis in tissues distantly located from the gut. In the mammary gland, CT pretreatment was shown to reduce tumor multiplicity, increase apoptosis and alter the expression of several cancer-related molecules.

Targeting EPHB2/ABL1 restores antitumor immunity in preclinical models of ependymoma.

Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.

The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity.

Tissue-resident memory T cells (TRM) provide frontline protection against pathogens and emerging malignancies. Tumor-infiltrating lymphocytes (TIL) with TRM features are associated with improved clinical outcomes. However, the cellular interactions that program TRM differentiation and function are not well understood.

CpG island methylator phenotype classification improves risk assessment in pediatric T-cell Acute Lymphoblastic Leukemia.

Current intensive treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has substantial side-effects, highlighting a need for novel biomarkers to improve risk stratification. Canonical biomarkers such as genetics and immunophenotype are largely not used in pediatric T-ALL stratification. This study aimed to validate the prognostic relevance of DNA methylation CpG island methylator phenotype (CIMP) risk stratification in two pediatric T-ALL patient cohorts: the Nordic NOPHO ALL2008 T-ALL study cohort (n=192) and the Dutch DCOG ALL-10/ALL-11 validation cohorts (n=156).

Irreversible Electroporation and β-Glucan Induced Trained Innate Immunity for the Treatment of Pancreatic Ductal Adenocarcinoma: A Phase II Study.

Introduction: Irreversible electroporation(IRE) has augmented the effects of certain immunotherapies in pancreatic cancer(PDA). Yeast-derived particulate beta-glucan induces trained innate immunity and has successfully reduces murine PC tumor burden. This is a Phase II study to test the hypothesis that IRE may augment beta-glucan induced trained immunity in patients with PDA.

Polymorphic Single-Nucleotide Variants in miRNA Genes and the Susceptibility to Colorectal Cancer: Combined Evaluation by Pairwise and Network Meta-Analysis, Thakkinstian's Algorithm and FPRP Criterium.

Background: Considerable epidemiological studies have examined the correlation between polymorphic single-nucleotide variants (SNPs) in miRNA genes and colorectal carcinoma (CRC) risk, yielding inconsistent results. Herein, we sought to systematically investigate the association between miRNA-SNPs and CRC susceptibility by combined evaluation using pairwise and network meta-analysis, the FPRP analysis (false positive report probability), and the Thakkinstian's algorithm.

Methods: The MEDLINE, EMBASE, WOS, and Cochrane Library databases were searched through May 2024 to find relevant association literatures.

Exploring Cervical Adenocarcinoma: Epidemiological Insights, Diagnostic and Therapeutic Challenges, and Pathogenetic Mechanisms.

Background: Cervical cancer poses a significant threat to women's health and encompasses various histological types, including squamous cell carcinoma (SCC), cervical adenocarcinoma (CA), and adenosquamous carcinoma. CA, in particular, presents a formidable challenge in clinical management due to its low early detection rate, pronounced aggressiveness, high recurrence rate, and mortality, compounded by the complexities associated with late-stage treatment. There is limited understanding of the similarities and differences in the pathogenesis mechanisms between CA and SCC, such as tumor heterogeneity and the tumor immune microenvironment (TME).

Relationship Between Short-Term Outcomes and PD-L1 Expression Based on Combined Positive Score and Tumor Proportion Score in Recurrent or Metastatic Head and Neck Cancers Treated With Anti-PD-1 Antibody Monotherapy.

Background: PD-L1 expression in tumors and immune cells is a biomarker for the efficacy of anti-PD-1 antibody (APA) therapy across diverse cancers. Based on the results from the KEYNOTE-048 trial, pembrolizumab monotherapy is indicated for platinum-sensitive recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC) with a positive combined positive score (CPS). Conversely, nivolumab is utilized for platinum-pretreated R/M-HNSCC regardless of the positive tumor proportion score (TPS) following the results of the CheckMate-141; however, its subgroup analysis indicated that TPS-positive population tended to have a relatively high overall response rate and progression-free survival (PFS).

The importance of preclinical models for cholangiocarcinoma drug discovery.

Introduction: Biliary tract cancer (BTC) comprises a clinically diverse and genetically heterogeneous group of tumors along the intra- and extrahepatic biliary system (intrahepatic and extrahepatic cholangiocarcinoma) and gallbladder cancer with the common feature of a poor prognosis, despite increasing molecular knowledge of associated genetic aberrations and possible targeted therapies. Therefore, the search for even more precise and individualized therapies is ongoing and preclinical tumor models are central to the development of such new approaches.

Areas Covered: The models described in the current review include simple and advanced in vitro and in vivo models, including cell lines, 2D monolayer, spheroid and organoid cultures, 3D bioprinting, patient-derived xenografts, and more recently, machine-perfusion platform-based models of resected liver specimens.

Peptide-Drug Conjugate for Therapeutic Reprogramming of Tumor-Associated Macrophages in Breast Cancer.

In triple-negative breast cancer (TNBC), pro-tumoral macrophages promote metastasis and suppress the immune response. To target these cells, a previously identified CD206 (mannose receptor)-binding peptide, mUNO was engineered to enhance its affinity and proteolytic stability. The new rationally designed peptide, MACTIDE, includes a trypsin inhibitor loop, from the Sunflower Trypsin Inhibitor-I.

Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

SOCS1 deficiency-crossroads of autoimmunity and autoinflammation-two case reports.

Suppressors of cytokine signaling (SOCS) proteins play a critical role in regulating immune signaling pathways. Deficiency of SOCS1 leads to various autoimmune pathologies. We present two unrelated patients with distinct clinical manifestations.

Virus-like particle: a nano-platform that delivers cancer antigens to elicit an anti-tumor immune response.

Virus-like particles (VLPs), as a unique form of nanocarrier, predominantly encompass hollow protein shells that exhibit analogous morphology and structure to naturally occurring viruses, yet devoid of genetic material. VLPs are considered safe, easily modifiable, and stable, making them suitable for preparation in various expression systems. They serve as precise biological instruments with broad applications in the field of medical biology.

Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC.

Introduction: The role of mast cells (MCs) in clear cell renal carcinoma (ccRCC) is unclear, and comprehensive single-cell studies of ccRCC MCs have not yet been performed.

Methods: To investigate the heterogeneity and effects of MCs in ccRCC, we studied single-cell transcriptomes from four ccRCC patients, integrating both single-cell sequencing and bulk tissue sequencing data from online sequencing databases, followed by validation via spatial transcriptomics and multiplex immunohistochemistry (mIHC).

Results: We identified four MC signature genes (TPSB2, TPSAB1, CPA3, and HPGDS).

VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens.

VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient's private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL's somatic mutations and human polymorphisms remain unexplored.

A novel oncolytic Vaccinia virus armed with IL-12 augments antitumor immune responses leading to durable regression in murine models of lung cancer.

Oncolytic vaccinia viruses (VVs) are potent stimulators of the immune system and induce immune-mediated tumor clearance and long-term surveillance against tumor recurrence. As such they are ideal treatment modalities for solid tumors including lung cancer. Here, we investigated the use of VVL-m12, a next-generation, genetically modified, interleukin-12 (IL-12)-armed VV, as a new therapeutic strategy to treat murine models of lung cancer and as a mechanism of increasing lung cancer sensitivity to antibody against programmed cell death protein 1 (α-PD1) therapy.

Integrating single cell analysis and machine learning methods reveals stem cell-related gene S100A10 as an important target for prediction of liver cancer diagnosis and immunotherapy.

Background: Hepatocellular carcinoma (LIHC) poses a significant health challenge worldwide, primarily due to late-stage diagnosis and the limited effectiveness of current therapies. Cancer stem cells are known to play a role in tumor development, metastasis, and resistance to treatment. A thorough understanding of genes associated with stem cells is crucial for improving the diagnostic precision of LIHC and for the advancement of effective immunotherapy approaches.

Hematopoietic stem cell transplantation as rescue therapy for refractory autoimmune retinopathy: a case report.

Autoimmune retinopathy (AIR) is a rare, potentially blinding retinal disease that remains a challenging condition to manage when resistant to conventional immune-modulatory approaches. We report clinical and electrophysiological improvement in a 49-year-old patient who underwent an autologous hematopoietic stem cell transplant (aHSCT) for thymoma-associated AIR after experiencing progressive disease despite receiving periocular and systemic steroids, mycophenolate mofetil, baricitinib, tacrolimus, bortezomib, rituximab, plasmapheresis, and intravenous immunoglobulin. The aHSCT had two stages: (i) peripheral blood stem cell harvest following mobilization with cyclophosphamide and granulocyte colony-stimulating factor, and (ii) conditioning regimen with plasmapheresis, rituximab, cyclophosphamide, and anti-thymocyte globulin high-dose therapy, followed by autologous hematopoietic cell infusion of 5.

Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer.

Background: Cervical cancer is the fourth most common cancer in women globally, and the main cause of the disease has been found to be ongoing HPV infection. Cervical cancer remains the primary cause of cancer-related death despite major improvements in screening and treatment approaches, especially in low- and middle-income nations. Therefore, it is crucial to investigate the tumor microenvironment in advanced cervical cancer in order to identify possible treatment targets.