Translational Health Reports

Abstract Background: Colorectal cancer (CRC) remains a major global health issue, with advanced stages difficult to treat. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have improved cancer care, but they work well only in a small group of CRC patients with high microsatellite instability (MSI-H). Most CRC cases are microsatellite stable (MSS) and do not respond to ICI treatment alone, highlighting the need for combined therapies.
Methods: This review summarizes recent studies from PubMed, Google Scholar, and clinical trial databases up to 2025 focusing on why CRC resists ICI treatment. It examines ways to modify the immunosuppressive tumor microenvironment (TME), including using immune-boosting agents and targeting proteins like USP2 that regulate PD-L1.
Results: The immunosuppressive TME in MSS-CRC limits the effectiveness of PD-1 blockers. Immune adjuvants, such as the peptide NCL-P2, can reshape the TME by activating immune cells, increasing T cell entry into tumors, and reducing T cell exhaustion. Additionally, recent studies show that USP2 helps stabilize PD-L1 in cancer cells. Blocking USP2 leads to PD-L1 breakdown, improving T cell attack and boosting anti-PD-1 therapy in lab studies.
Conclusion: Combining anti-PD-1 antibodies with treatments that alter the immunosuppressive TME—such as immune adjuvants to strengthen immune responses and USP2 inhibitors to lower PD-L1 levels—offers a promising multi-target strategy. This method could help overcome treatment resistance and extend immunotherapy benefits to more CRC patients.

Abstract Background: Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease with an incompletely understood etiology. Observational studies suggest dysregulated immunity, but confounding and reverse causation have hindered causal inference. Mendelian randomization (MR) uses genetic variants as instrumental variables to assess causality and has recently been applied to investigate immune involvement in AIH.
Objective: To summarize and interpret findings from a recent bidirectional two-sample MR study evaluating the causal effects of 731 immune cell traits on AIH risk, contextualizing them within existing immunological knowledge.
Methods: This narrative review focuses on a key MR investigation using genome-wide association study (GWAS) summary statistics for 731 immunophenotypes and AIH. The primary analysis method was inverse variance weighting, supplemented by sensitivity analyses (MR-Egger, weighted median) and reverse MR to assess robustness and directionality of causal relationships.
Conclusion: The MR analysis provides genetic evidence supporting a causal role for specific innate and adaptive immune cell subsets in AIH pathogenesis. These findings highlight the therapeutic potential of targeting pathways involving myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), dendritic cells, NKT cells, and the PD-1/PD-L1 axis, offering a foundation for future mechanistic and translational research.
 

Abstract Background: Neoadjuvant chemotherapy is a common treatment approach for breast cancer, but its impact on disease-free survival, quality of life, and recurrence rates is not well understood.

Objectives: To evaluate the association between neoadjuvant chemotherapy and disease-free survival, quality of life, and recurrence rates in patients with breast cancer.

Methods: This retrospective cohort study included 350 patients with breast cancer who underwent surgery at a university clinic between 2015 and 2022. Patients were divided into two groups: those who received neoadjuvant chemotherapy (n=105) and those who did not (n=245). Demographic, tumor, and treatment characteristics were compared between groups. Disease-free survival, quality of life, and recurrence rates were analyzed using Cox proportional hazards models, multivariate analysis of variance, and logistic regression models. 1 year follow ups were made.

Results: Patients who received neoadjuvant chemotherapy had a significant reduction in the risk of disease recurrence (HR=0.65, p=0.02) and local recurrence (OR=0.42, p=0.01). However, they had lower physical and social functioning scores compared to those who did not receive neoadjuvant chemotherapy (p=0.04 and p=0.02, respectively). Neoadjuvant chemotherapy was also associated with a higher survival rate at 12 months (92.5% vs. 85.1%, p=0.03).

Conclusions: Neoadjuvant chemotherapy is associated with improved disease-free survival and reduced local recurrence rates in patients with breast cancer. However, it may have a negative impact on quality of life, particularly physical and social functioning. These findings have implications for the management of breast cancer and highlight the need for further research on the optimal use of neoadjuvant chemotherapy.

Abstract Background: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Radiation therapy (RT) and temozolomide (TMZ) are standard treatments, but their impact on cognitive function is not well understood.

Objective: To investigate the effects of radiation dose and TMZ dose on cognitive function in patients with GBM treated with RT and TMZ.

Methods: This retrospective study included 162 patients with GBM treated with RT and TMZ between 2018 and 2023. Cognitive function was assessed using a comprehensive battery of neuropsychological tests, and MRI-based measures of cognitive function were obtained. Patients were categorized into three groups based on radiation dose received: low dose (< 50 Gy), moderate dose (50-60 Gy), and high dose (> 60 Gy). Follow ups were made up to 8 to 12 months after chemoradiotherapy.

Results: Patients in the high dose group performed significantly worse on executive function and memory tests, and had reduced white matter integrity and increased white matter hyperintensity volume compared to the low dose group. Higher TMZ doses were associated with poorer cognitive outcomes in executive function, memory, and reduced hippocampal volume. Linear regression analysis showed that higher radiation doses were associated with poorer cognitive outcomes in memory, and higher TMZ doses were associated with poorer cognitive outcomes in executive function, memory, and reduced hippocampal volume.

Conclusion: This study suggests that higher radiation doses and TMZ doses are associated with poorer cognitive outcomes in patients with GBM. These findings have important implications for the management of GBM, highlighting the need to minimize radiation dose and TMZ dose to prevent cognitive decline. Future studies are needed to confirm these findings and to explore strategies to mitigate the cognitive effects of RT and TMZ in patients with GBM.