Immune Profiling in Gastric Cancer Reveals the Dynamic Landscape of Immune Signature Underlying Tumor Progression.

The profiling of the tumor immune microenvironment (TIME) is critical for guiding immunotherapy strategies. However, how the composition of the immune landscape affects the tumor progression of gastric cancer (GC) is ill-defined. Here, we used mass cytometry to perform simultaneous in-depth immune profiling of the tumor, adjacent tissues, and blood cells from GC patients and revealed a unique GC tumor-immune signature, where CD8+ T cells were present at a lower frequency in tumor tissues compared to adjacent tissues, whereas regulatory T cells and tumor-associated macrophages (TAMs) were significantly increased, indicating strong suppressive TIME in GC. Incorporated with oncogenic genomic traits, we found that the unique immunophenotype was interactively shaped by a specific GC gene signature across tumor progression. Earlier-stage GC lesions with IFN signaling enrichment harbored significantly altered T-cell compartments while advanced GC featured by metabolism signaling activation was accumulated by TAMs. Interestingly, PD-1 expression on CD8+ T cells was relatively higher in earlier-stage GC patients, indicating that these patients may derive more benefits from PD-1 inhibitors. The dynamic properties of diverse immune cell types revealed by our study provide new dimensions to the immune landscape of GC and facilitate the development of novel immunotherapy strategies for GC patients.

Systematic review and meta-analysis of the incidence rates of adverse events after digestive endoscopy in children.

Background: With the widespread use of digestive endoscopy in children, a variety of adverse events (AEs) have occurred after digestive endoscopy. However, there are notable differences in the incidence of adverse reactions in digestive endoscopy in children at present, which makes it difficult to assess the safety of digestive endoscopy in children. Methods: Studies related to digestive endoscopy in children were screened from January 2005 to October 2021 from PubMed, Web of Science, Spring, CNKI, and Science Direct databases. RevMan5.3 and Stata were employed to carry out meta-analysis on the incidence of adverse respiratory events, myoclonus, abdominal pain, fever, bleeding, chest pain, sore throat, vomiting, and delayed capsule discharge after digestive endoscopy in children. The article quality was evaluated by the Agency for Healthcare Research and Quality (AHRQ). The chi-square test and I2 were adopted to test literature heterogeneity, and the article publication bias was assessed by displaying an inverted funnel plot as a funnel plot. Results: In all, 15 articles were included, involving a total of 27,770 children. In all, 15 articles were included, involving a total of 27,770 children. The risk ratio (RR) value of adverse respiratory events after digestive endoscopy in children was 1.31 [95% confidence interval (CI): 1.17 to 1.47, P<0.00001]; the odds ratio (OR) value of the incidence of myoclonus was 1.21 (95% CI: 1.01 to 1.46, P=0.04); the incidence of abdominal pain was 1.18 (95% CI: 1.11 to 1.27, P<0.00001); the incidence of fever was 1.09 (95% CI: 1.06 to 1.12, P<0.00001); the incidence of bleeding was 1.24 (95% CI: 0.94 to 1.64, P=0.13); the incidence of chest pain was 1.06 (95% CI: 1.03 to 1.09, P<0.0001); incidence of sore throat was 1.11 (95% CI: 1.05 to 1.18, P=0.0004); incidence of vomiting was 1.13 (95% CI: 1.06 to 1.21, P=0.0001); and the incidence of delayed capsule expulsion was 1.18 (95% CI: 1.00 to 1.40, P=0.05). Discussion: The incidence of AEs after digestive endoscopy in children was low, which can be used in the diagnosis and therapy of digestive system diseases in children.

Effect of predictive trauma care on fracture healing and complications of traumatic fracture patients in emergency department.

OBJECTIVE: To explore the advantages of predictive trauma care in fracture healing and prevention of complications in patients with traumatic fracture. METHODS: Through prospective research methods, 80 patients with traumatic fractures were divided into a research group and a control group, each with 40 cases. The control group was given regular emergency care, while the research group was given predictive trauma care. The related clinical indicators, complications and scores on changes in joint range of motion (ROM), mental status and quality of life before and after intervention were compared between the two groups. RESULTS: Compared with the control group, the time of pain relief, fracture recovery and hospital stay of the research group was significantly shortened (all P<0.01). The overall incidence of complications in the research group was lower than that in the control group (5.00% vs 20.00%, P<0.05). For patients with limb fractures, the ROM scores of the two groups after intervention were significantly higher than those before intervention, and the scores of the research group were higher than those of the control group (all P<0.05). Compared with the condition before intervention, the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores of the two groups of patients were significantly reduced after intervention, and the scores of research group were lower than those of the control group (all P<0.05). Compared with the condition before intervention, the scores of physical function, social function, psychological function and daily life condition of the two groups of patients were significantly increased 3 months after discharge from hospital, and the scores of the research group were significantly higher than those of the control group (all P<0.05). CONCLUSION: Predictive trauma care can effectively reduce the risk of postoperative complications in patients with traumatic fractures, promote the fracture healing, relieve the patients' anxiety and depression, and improve their quality of life.

The impaired anti-tumoral effect of immune surveillance cells in the immune microenvironment of gastric cancer.

Immune surveillance cells in the tumor microenvironment play an important role in inhibiting tumorigenesis and metastasis, but their anti-tumoral effects are impaired. The anti-tumoral effects of innate immune cells and adaptive immune cells in the immune microenvironment of gastric cancer are also impaired. Their degree of functional impairment is closely related to the prognosis of gastric cancer. Multiple factors inhibit the anti-tumoral effects of immune surveillance cells, such as decreased numbers of immune surveillance cells, reduced activating receptors, decreased secretion of pro-inflammatory cytokines, increased apoptosis, elevated expression of coinhibitory molecules on cancer cells or immunosuppressive cells, increased secretion of inhibitory cytokines, impaired antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by antigen-presenting cells (APCs) and pro-tumoral polarization of cells with functional plasticity. These factors can potentially combine to suppress the immune surveillance cells' functions. However, there are conflicting conclusions on the effects of immune surveillance cells on gastric cancer cells. These contradictions are partly due to the heterogeneity of the tumor microenvironment.

DNT Cell-based Immunotherapy: Progress and Applications.

Cancer immunotherapy has firmly established a dominant status in recent years. Adoptive cellular immunotherapy (ACI) is the main branch of immunotherapy. Recently, the immune effector cells of ACI, such as T cells, NK cells, and genetically engineered cells, have been used to achieve significant clinical benefits in the treatment of malignant tumors. However, the clinical applications have limitations, including toxicity, unexpectedly low efficiency, high costs and strict technical requirements. More exploration is needed to optimize ACI for cancer patients. CD3+CD4-CD8- double negative T cells (DNTs) have emerged as functional antitumor effector cells, according to the definition of adoptive immunotherapy. They constitute a kind of T cell subset that mediates nontumor antigen-restricted immunity and has important immune regulatory functions. Preclinical experiments showed that DNTs had a dual effect by killing tumor cells and inhibiting graft-versus-host disease. Notably, DNTs can be acquired from healthy donors and expanded in vitro; thus, allogeneic DNTs may be provided as "off-the-shelf" cellular products that can be readily available for direct clinical application. We review the progress and application of DNTs in immunotherapy. DNTs may provide some novel perspectives on cancer immunotherapy.

Efficacy and safety of combination immunotherapy for malignant solid tumors: A systematic review and meta-analysis.

BACKGROUND: Combination immunotherapy has become an actively growing field of clinical investigation. METHODS: We searched for clinical trials of combination immunotherapy and calculated the pooled hazard ratio (HR), odds ratio (OR) of clinical outcomes and safety by subgroups of different combination regimens. RESULTS: Totally 28 clinical trials were analyzed. The study showed that the pooled HRs of overall survival and progression-free survival for combination therapy were 0.77 (95% CI: 0.70-0.84, p < 0.001) and 0.72 (95% CI: 0.66-0.79, p < 0.001) while the pooled OR of high-grade adverse effects was 1.45 (p = 0.004). Subgroup analysis showed that the HR of overal survival were 0.74 (p = 0.005), 0.79 (p < 0.001), 0.70 (p = 0.003) and 0.85 (p = 0.052) for immunotherapy combined with immunotherapy, chemotherapy, targeted therapy and radiotherapy group, respectively. CONCLUSIONS: The meta-analysis indicated that combination immunotherapy could bring more clinical benefits with increased high-grade adverse effects.

Clinical outcomes comparison of 10 years versus 5 years of adjuvant endocrine therapy in patients with early breast cancer.

BACKGROUND: Adjuvant endocrine therapy undoubtedly prolongs the time to recurrence for patients with hormone-positive early breast cancer. Extended endocrine therapy to 10 years or longer has been expected to bring a greater clinical advantage. However, the related research conclusions are controversial. METHODS: Tamoxifen (TAM), Aromatase Inhibitor (AI), Exemestane, letrozole (LET) and anastrozole were used as key words in the literature search. After the patients completed 5 years of adjuvant endocrine treatment, they were allocated to continue endocrine treatment for 5 years or receive placebo/observation for 5 years. Disease-free survival (DFS) and overall survival (OS) were the end points. Systematic assessment was performed using Stata 12.0. RESULTS: Twelve trials including 30,848 cases were involved. The overall analysis demonstrated that extended endocrine therapy to 10 years significantly prolonged DFS compared with 5 years of endocrine therapy [hazard ratio (HR) = 0.84, 95% CI: 0.73-0.97]. Subgroup analysis showed that DFS was significant prolonged with TAM 5y - AI 5y treatment versus TAM 5y treatment and with (AI and/or TAM) 5y - LET 5y treatment versus (AI and/or TAM) 5y treatment [(HR = 0.61, 95% CI: 0.50-0.76) and (HR = 0.81, 95% CI: 0.71-0.93), respectively]. However, no significant difference was found in the DFS with TAM 5y - TAM 5y treatment versus TAM 5y treatment (HR = 0.97, 95% CI: 0.81-1.17). Overall and subgroup analysis did not demonstrate an OS benefit of therapy extended to 10 years. A DFS benefit of extended endocrine therapy to 10 years was verified in the lymph node-positive subgroup, postmenopausal subgroup and ER+ and/or PR+ subgroup (HR = 058, 95% CI: 0.45-0.75; HR = 0.70, 95% CI: 0.58-0.80; HR = 0.80, 95% CI: 0.67-0.96). CONCLUSIONS: An extended 10 years of endocrine treatment yields a DFS benefit for patients with early breast cancer; (AI and/or TAM) 5y - AI 5y treatment is the optimal choice. ER+ and/or PR+, postmenopausal and lymph node-positive patients are the most suitable groups.