From PD-1/PD-L1 to tertiary lymphoid structures: Paving the way for precision immunotherapy in cholangiocarcinoma treatment.

Cholangiocarcinoma (CCA) is a highly malignant hepatobiliary tumor characterized by limited treatment options and poor prognosis. The recent rise of immunotherapy has significantly influenced research in this field. This study presents a bibliometric analysis of 416 articles retrieved from the WOSCC, Wan fang Data, CNKI and VIP databases, spanning contributions from 32 countries, 589 institutions and 3,200 authors.

Clinical significance of upregulated Rho GTPase activating protein 12 causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a major health challenge with high incidence and poor survival rates in China. Systemic therapies, particularly tyrosine kinase inhibitors (TKIs), are the first-line treatment for advanced HCC, but resistance is common. The Rho GTPase family member Rho GTPase activating protein 12 (ARHGAP12), which regulates cell adhesion and invasion, is a potential therapeutic target for overcoming TKI resistance in HCC.

Targeting tumor-infiltrating tregs for improved antitumor responses.

Immunotherapies have revolutionized the landscape of cancer treatment. Regulatory T cells (Tregs), as crucial components of the tumor immune environment, has great therapeutic potential. However, nonspecific inhibition of Tregs in therapies may not lead to enhanced antitumor responses, but could also trigger autoimmune reactions in patients, resulting in intolerable treatment side effects.

MNK: A Novel Promising Target for Cancer Immunotherapy.

Cancer immunotherapy has demonstrated remarkable success in the treatment of multiple advanced malignancies, especially approaches to target the immune checkpoint. Nonetheless, the limited response rate remains a barrier to broader application. Identifying other ways to extend the beneficiaries to a large extent is needed.

Exploring CAR-T Cell Therapy Side Effects: Mechanisms and Management Strategies.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of malignancies, especially hematological tumors, but toxicities have tempered its success. The main impediments to the development of CAR-T cell therapies are the following: cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and on-target/off-tumor toxicity (OTOT). This review summarizes these side effects' underlying mechanisms and manifestations over time.

Targeting sphingosine 1-phosphate receptor 3 inhibits T-cell exhaustion and regulates recruitment of proinflammatory macrophages to improve antitumor efficacy of CAR-T cells against solid tumor.

Backgrounds: Chimeric antigen receptor (CAR)-modified T cells (CAR-T) are limited in solid tumors due to the hostile tumor microenvironment (TME). Combination therapy could be a promising approach to overcome this obstacle. Recent studies have shown that sphingosine 1-phosphate receptor (S1PR)3 has tremendous potential in regulating the immune environment.

Optimized CAR-T therapy based on spatiotemporal changes and chemotactic mechanisms of MDSCs induced by hypofractionated radiotherapy.

Poor intratumoral infiltration is the major challenge for chimeric antigen receptor (CAR)-T cell therapy in solid tumors. Hypofractionated radiotherapy (HFRT) has been reported to induce immune cell infiltration and reshape the tumor immune microenvironment. Here, we showed that HFRT (5 × 5 Gy) mediated an early accumulation of intratumoral myeloid-derived suppressor cells (MDSCs) and decreased infiltration of T cells in the tumor microenvironment (TME) of immunocompetent mice bearing triple-negative breast cancer (TNBC) or colon cancer, which was further confirmed in tumors from patients.

gC1qR: A New Target for Cancer Immunotherapy.

Although breakthroughs in cancer treatment have been achieved, immunotherapy yields only modest benefits in most patients. There is still a gap in clarifying the immune evasiveness and immune-resistance mechanisms. Identifying other candidate targets for cancer immunotherapy is therefore a clear unmet clinical need.

Clustering Deviation Index (CDI): a robust and accurate internal measure for evaluating scRNA-seq data clustering.

Most single-cell RNA sequencing (scRNA-seq) analyses begin with cell clustering; thus, the clustering accuracy considerably impacts the validity of downstream analyses. In contrast with the abundance of clustering methods, the tools to assess the clustering accuracy are limited. We propose a new Clustering Deviation Index (CDI) that measures the deviation of any clustering label set from the observed single-cell data.

A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis.

Pleural and peritoneal metastasis accompanied by malignant pleural effusion (MPE) or malignant ascites (MA) is frequent in patients with advanced solid tumors that originate from the lung, breast, gastrointestinal tract and ovary. Regional delivery of CAR-T cells represents a new strategy to control tumor dissemination in serous cavities. However, malignant effusions constitute an immune-suppressive environment that potentially induces CAR-T cell dysfunction.

Cancer-cell-derived GABA promotes β-catenin-mediated tumour growth and immunosuppression.

Many cancers have an unusual dependence on glutamine. However, most previous studies have focused on the contribution of glutamine to metabolic building blocks and the energy supply. Here, we report that cancer cells with aberrant expression of glutamate decarboxylase 1 (GAD1) rewire glutamine metabolism for the synthesis of γ-aminobutyric acid (GABA)-a prominent neurotransmitter-in non-nervous tissues.

Neurotoxicity of Tumor Immunotherapy: The Emergence of Clinical Attention.

Tumor immunotherapy brings substantial and long-term clinical benefits that can even cure tumors. However, the accumulation of evidence suggests that immunotherapy also induces severe and complex neurologic immune-related adverse events (ir-AEs) and even leads to immunotherapy-related death, which arouses the concern of clinicians. The timely and accurate identification of neurotoxicity helps clinicians detect and treat these complications early, thereby enhancing treatment efficiency and improving the prognosis of patients.

Peripheral eosinophil counts predict efficacy of anti-CD19 CAR-T cell therapy against B-lineage non-Hodgkin lymphoma.

The onset of cytokine release syndrome (CRS) and persistence of anti-CD19 chimeric antigen receptor T (CAR-T) cells after infusion correlate with clinical responsiveness. However, there are no known baseline biomarkers that can predict the prognosis of patients with B-lineage non-Hodgkin lymphoma (B-NHL). The aim of this study was to identify blood cell populations associated with beneficial outcomes in B-NHL patients administered CAR-T cell immunotherapies.

Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models.

The tumoricidal efficiency of human CAR-T cells is generally evaluated using immune-deficient mouse models; however, due to their immune-incompetency and the species-specific reactivity of a target antigen, these models are problematic to imitate CAR-T-induced adverse effects in the clinic. Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen overtly presented on the cell surface of various carcinomas, making it an attractive target for CAR-T therapy. Here, we developed an anti-mouse EpCAM CAR to evaluate its safety and efficacy in immunocompetent mouse models.

Low-Dose Radiation Therapy Promotes Radiation Pneumonitis by Activating NLRP3 Inflammasome.

Purpose: To determine the role of NLRP3 inflammasome activation in low-dose radiation-induced radiation pneumonitis (RP) and to assess whether inhibition or deletion of the NLRP3 inflammasome is critical for conferring protection against RP.

Methods And Materials: The human monocytic THP-1 cells were treated with increasing doses of radiation to assess the activation of NLRP3 by Western blot and enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) production was measured by flow cytometry, with or without ROS inhibitor treatment.

An elderly female patient with ROS1 rearrangement primary lung adenocarcinoma and breast carcinoma: a rare case report and review of the literature.

We report the case of a 90-year-old female patient who was suffering from c-ros oncogene 1 () rearrangement adenocarcinoma and breast cancer. After about 14 months of a reduced dose of crizotinib treatment, she had a stable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.

[The Construction of ROR1 Targeting Chimeric Antigen Receptor Modified T Cells and Its Killing Effect for ROR1-positive Tumor Cells].

Objective: To test the killing effect of type Ⅰ receptor tyrosine kinase-like orphan receptor (ROR1) chimeric antigen receptor T cell (CAR-T) on several ROR1-expressing tumor cells

Methods: The CAR gene was designed and synthesized by constructing the lentiviral vector plasmid, and HⅠ/RⅠ was used to identify the plasmid. The expression levels of ROR1 among a variety of tumor cell lines were compared using flow cytometry (FCM). The killing effect of CAR-T on positive cells was detected by FCM, the LDH assay and ELISA.

Preclinical Evaluation of Chimeric Antigen Receptor-Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer.

Chimeric antigen receptor-modified T cells (CAR-T cells) have emerged as a promising cancer immunotherapy for solid tumors. Epithelial cell adhesion molecule (EpCAM) is overexpressed in a variety of tumors and is recognized as a biomarker for circulating tumor cells and cancer stem cells, representing an attractive target for adoptive T-cell immunotherapy. This study generated third-generation CAR-T cells with redirected specificity to EpCAM (EpCAM CAR-T) by lentiviral vector.

Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells.

Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection. This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia, whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8 T cell responses against pathogens in treatment-naive mice bearing large tumors.

Paralleled comparison of vectors for the generation of CAR-T cells.

T-lymphocytes genetically engineered with the chimeric antigen receptor (CAR-T) have shown great therapeutic potential in cancer treatment. A variety of preclinical researches and clinical trials of CAR-T therapy have been carried out to lay the foundation for future clinical application. In these researches, several gene-transfer methods were used to deliver CARs or other genes into T-lymphocytes, equipping CAR-modified T cells with a property of recognizing and attacking antigen-expressing tumor cells in a major histocompatibility complex-independent manner.

Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors.

Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity.

Establishing guidelines for CAR-T cells: challenges and considerations.

T cells, genetically modified by chimeric antigen receptors (CAR-T), are endowed with specificity to a desired antigen and are cytotoxic to cells expressing the targeted antigen. CAR-T-based cancer immunotherapy is a promising therapy for curing hematological malignancy, such as acute lymphoid leukemia, and is promising for extending their efficacy to defeat solid tumors. To date, dozens of different CAR-T cells have been evaluated in clinical trials to treat tumors; this necessitates the establishment of guidelines for the production and application of CAR-T cells.

Impact of parental-rearing styles on irritable bowel syndrome in adolescents: a school-based study.

Background And Aim: A strong association between family function and irritable bowel syndrome (IBS) has been observed. Parental rearing styles, as a comprehensive mark for family function, may provide new clues to the etiology of IBS. This study aimed to explore which dimensions of parental rearing styles were risk factors or protective factors for IBS in adolescents.