Gastric cancer is a malignant tumor that ranks third in cancer-related deaths worldwide. Early-stage gastric cancer can often be effectively managed through surgical resection. However, the majority of cases are diagnosed in advanced stages, where outcomes with conventional radiotherapy and chemotherapy remain unsatisfactory. Immunotherapy offers a novel approach to treating molecularly heterogeneous gastric cancer by modifying the immunosuppressive tumor microenvironment. Immune checkpoint inhibitors and adoptive cell therapy are regarded as promising modalities in cancer immunotherapy. Food and Drug Administration-approved programmed death-receptor inhibitors, such as pembrolizumab, in combination with chemotherapy, have significantly extended overall survival in gastric cancer patients and is recommended as a first-line treatment. Despite challenges in solid tumor applications, adoptive cell therapy has demonstrated efficacy against various targets in gastric cancer treatment. Among these approaches, chimeric antigen receptor-T cell therapy research is the most widely explored and chimeric antigen receptor-T cell therapy targeting claudin18.2 has shown acceptable safety and robust anti-tumor capabilities. However, these advancements primarily remain in preclinical stages and further investigation should be made to promote their clinical application. This review summarizes the latest research on immune checkpoint inhibitors and adoptive cell therapy and their limitations, as well as the role of nanoparticles in enhancing immunotherapy.

Background: The prevalence of myopia is increasing dramatically around the world, and many studies have suggested the possibility that ultraviolet (UV) light is effective to prevent the onset and progression of myopia. However, UV is a risk factor for diseases that cause refractive errors such as cataract and pterygium. In this study, we evaluated the relationship between UV exposure and myopia progression.

Methods: The dataset consisted of a total of 337 396 eyes of patients in the 12-to-29-year age range, who were prescribed soft contact lenses (SCL) for refractive error at Okada Eye Clinic in Japan between 2002 and 2011. They were tracked over a five-year period and did not change the type of SCL. In this retrospective cohort study based on medical records, we divided patients into two groups, one prescribed SCL with UV protection (UV-SCL), and another prescribed SCL without UV protection (UV + SCL).

Results: Change in refractive power over five years was measured and results compared. It was −0.413 diopter (D) in the UV-SCL group and −0.462 D in the UV + SCL group. Thus, the progression of myopia was slower in the UV-SCL group. The results were also analyzed separately by gender and degree of myopia at the time of initial prescription, which all showed significant differences (P< 0.001).

Conclusion: Results suggest that UV exposure may advance myopia. Further research is needed to investigate the underlying mechanisms that could explain this.

Background: Infantile hemangioma (IH) is the most prevalent benign vascular tumor in children, yet its pathogenesis remains incompletely understood. Research has established a strong association between SOX4 and tumor blood vessel formation. The objective of this study was to investigate the function and underlying mechanism of SOX4 in IH development with the aim of identifying novel therapeutic targets.

Methods: We identified the transcription factor SOX4 associated with IH through RNA-seq screening of IH microtumors and validated it in IH tissues. The effect of SOX4 on the biological behavior of CD31+ hemangioma-derived endothelial cells (HemECs) was investigated via in vitro cell experiments. In addition, RNA-seq analysis was performed on CD31+ HemECs with low expression levels of SOX4, and the target genes of SOX4 were identified. Finally, the effect of SOX4 on tumor angiogenesis was further elucidated through 3D microtumor and animal experiments.

Results: SOX4 is highly expressed in IH tissues and promotes the proliferation, migration, and angiogenesis of CD31+ HemECs. In addition, SOX4 binds to the endothelial cell-specific molecule 1 (ESM1) promoter to promote the progression of the PI3K/AKT signaling pathway. Finally, through IH 3D microtumor and animal experiments, SOX4 and ESM1 are shown to be tumorigenic genes that independently promote tumor progression.

Conclusions: SOX4 plays a crucial role in the progression of IH, and the SOX4/ESM1 axis may serve as a novel biomarker and potential therapeutic target for IH.

Background: Both intestinal and pulmonary systems are parts of the mucosal immune system, comprising ∼80% of all immune cells. These immune cells migrate or are transported between various mucosal tissues to maintain tissue homeostasis.

Methods: In this study, we isolated neutrophils from the peripheral blood of patients and utilized immunofluorescence, flow cytometry, and Western blotting to confirm the incidence of “nucleus-directed degranulation” in vitro. Subsequently, we conducted a precise analysis using arivis software. Furthermore, using the DSS mouse model of colitis and tissue clearing technologies, we validated the “targeted nuclear degranulation” of neutrophils and their migration to the lungs in an inflammatory intestinal environment.

Result: In this study, we found that among patients with ulcerative colitis, the migration of neutrophils with “targeted nuclear degranulation” from the intestinal mucosa to the lungs significantly exacerbates lung inflammation during pulmonary infections. Notably, patients with ulcerative colitis exhibited a higher abundance of neutrophils with targeted nuclear degranulation. Using DSS mice, we observed that neutrophils with targeted nuclear degranulation from the intestinal mucosa migrated to the lung and underwent activation during pulmonary infections. These neutrophils rapidly released a high amount of neutrophil extracellular traps to mediate the progression of lung inflammation. Alterations in the neutrophil cytoskeleton and its interaction with the nuclear membrane represent the primary mechanisms underlying targeted nuclear degranulation.

Conclusion: This study revealed that neutrophils accelerate lung inflammation progression in colitis, offering new insights and potential treatment targets for lung infections for patients with colitis.

Background: Tertiary lymphoid structures (TLS) are major components in the immune microenvironment, correlating with a favorable prognosis in colorectal cancer. However, the methods used to define and characterize TLS were not united, hindering its clinical application. This study aims to seek a more stable method to characterize TLS and clarify their prognostic value in larger multicenter cohorts.

Methods: A total of 1609 patients from four hospitals and The Cancer Genome Atlas database were analyzed. We quantified the number and maximum length of TLS along the invasive margin of tumor using hematoxylin and eosin-stained whole-slide images (WSIs). Additionally, the length of the invasive margin was determined to calculate the TLS density. The prognostic value of TLS for overall survival was evaluated. In addition, we examined the association between TLS density and immune cell infiltration using immunohistochemistry-stained WSIs. The performance for predicting overall survival was measured using hazard ratios (HR) with 95% confidence intervals (CI).

Results: Among the three TLS quantification methods, TLS density has the strongest discriminative performance. Survival analysis indicated that higher TLS density correlated with better overall survival [HR for high vs. low 0.57 (95% CI 0.42-0.78) in the primary cohort; 0.49 (0.35-0.69) in the validation cohort; 0.35 (0.18-0.67) in TCGA cohort]. A high TLS density was associated with a high level of CD3⁺ T cell infiltration.

Conclusions: Based on this comparative multicenter analysis, TLS density was identified as a simple, robust, and effective immune prognostic index for colorectal cancer.