Clinical & Translational Oncology最新文献

Background: Immunosuppression might increase the risk of skin cancer in organ transplant recipients (OTRs), with azathioprine (AZA), exerting a fundamental role in the carcinogenesis of those tumors. This systematic review and meta-analysis aims to address the risk of developing malignant skin neoplasms in OTRs undergoing immunosuppression with AZA.

Methods: PubMed, Cochrane and Embase were searched for studies with OTRs who have a treatment regimen involving Azathioprine therapy after transplantation and that analyzed the emergence of skin neoplasia. We performed the meta-analysis using RStudio v4.4.2 software.

Results: A total of 17 studies comprising a total of 12,708 patients were included, of whom 3567 (28,06%) had a treatment regimen involving AZA therapy after transplantation. The majority of individuals were male 7298 (56,52%) and the median age of patients ranged from 41.5 to 63.2 years. The overall summary estimate showed a significantly increased risk of all types of skin cancer in relation to AZA exposure (OR 1.55; 95% CI 1.07-2.25; p = 0.018; I² = 82%). These results show that the overall result is statistically significant, which means that the observed effect is unlikely to be caused by chance.

Conclusion: This study highlights the increased risk of developing skin cancer, particularly squamous cell carcinoma (SCC), in OTRs receiving immunosuppressive therapy with AZA, which allows for rigorous screening and appropriate preventive and therapeutic interventions.

Introduction: The transporter associated with antigen processing (TAP) is a key component of the classical HLA I antigen presentation pathway. Our previous studies have demonstrated that the downregulation of TAP1 contributes to tumor progression and is associated with an increased presence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. However, it remains unclear whether the elevation of MDSCs leads to immune cell exhaustion in tumors lacking TAP1. In this study, we established mouse models of tumors with TAP1 deficiency, and we employed PMN-MDSC depletion to investigate their impact on the immune microenvironment within the tumors. We found that MDSC depletion significantly altered the immune-suppressive effects of TAP1-deficient tumor when anti-PD-1 treatment was administered. Targeting PMN-MDSC may be a promising therapeutic strategy for the treatment of tumors with TAP1 deficiency during ICB treatment.

Methods: Immunohistochemistry (IHC) was conducted to assess TAP1 expression in mouse melanoma tissues. Ly6G, F4/80, and NKp46 markers were detected in B16 parental and TAP1 knockout tissues, respectively. To enhance anti-tumor immunity, hyperthermia-treated B16F10 WT cell suspension was injected prior to tumor cell introduction. Subsequently, we established B16F10 TAP1 knockout and WT melanoma mouse models. Tumors were collected, and the immune microenvironment was monitored accordingly. Anti-Ly6G antibody was administered to deplete polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Finally, flow cytometry analysis for immune infiltration, quantitative PCR for cytokine levels, and immunofluorescence assays were performed to analyze the immune response.

Results: The level of Ly6G+ cell infiltration was significantly higher in samples exhibiting low TAP1 expression, while no differences were observed in the infiltration of F4/80+ cells or NKp46+ cells. Furthermore, the immune-suppressive effects associated with PMN-MDSCs were reversed following their elimination; this resulted in an increase in CD8+ T cells and a higher ratio of CD8+ T cells to Tregs, while the infiltration of innate immune cells remained unaffected. Functional markers of these immune cells indicated an active anti-tumoral immune response following the removal of PMN-MDSCs. Quantitative PCR analysis indicated elevated levels of TNF-α and IL-6, accompanied by decreased levels of TGF-β in the tumor microenvironment of TAP1.

Conclusions: Our data indicate that myeloid-derived suppressor cells (PMN-MDSCs) play an essential role in creating a tumorigenic immune microenvironment in TAP1 knockout tumors. Therefore, targeting PMN-MDSCs may become a promising therapeutic strategy for the treatment of tumors with TAP1 deficiency during ICB treatment.

Males have a higher incidence and mortality rate from colorectal cancer (CRC) compared with females. This review examines the reasons for these differences, including risk factors, screening participation, interpretation of screening tests, presentation and tumour types, pathophysiology (particularly the impact of sex hormones on tumour-related gene expression, microsatellite instability, micro-RNA expression, and the tumour microenvironment), and the efficacy and toxicity of treatment. Sex differences in hormones and body composition are responsible for some of the sexual dimorphism in CRC incidence and outcomes, particularly the pathophysiology, CRC presentation, the pharmacokinetics of cytotoxic therapies, and the impact of treatment on outcomes. However, gender differences also play a role, affecting risk factors, access to or participation in screening and treatment, and patients' experience of treatment (e.g. adverse events and sequelae). Sex and gender issues warrant further investigation in CRC to optimise treatment outcomes for patients.

Purpose: Identifying prognostic indicators for risk stratification in metastatic renal cell carcinoma (mRCC) is crucial for optimizing treatment strategies and follow-up plans. This study aims to investigate the prognostic role of the glucose-to-lymphocyte ratio (GLR) in patients with mRCC receiving tyrosine kinase inhibitors (TKIs) as first-line therapy.

Methods: A retrospective cohort study was conducted using data from the Turkish Oncology Group Kidney Cancer Consortium Database. GLR was calculated by dividing the fasting glucose (mmol/L) by the lymphocyte count (×10⁹/L). We categorized patients into two categories based on their median GLR level.

Results: The analysis included a total of 598 patients. We found that progression-free survival (PFS) was significantly longer in the GLR-low group, with a median PFS of 15.05 months (95% CI 12.7-17.4) compared to 7.79 months (95% CI 6.6-9.0) in the GLR-high group (p < 0.001). Multivariate analysis identified GLR as an independent risk factor for poor PFS (HR 1.39, 95% CI 1.12-1.72; p = 0.003). Overall survival (OS) was also significantly longer in the GLR-low group, with a median OS of 38.47 months (95% CI, 30.9-46.0) compared to 24.15 months (95% CI 18.0-30.2) in the GLR-high group (p = 0.001). GLR was an independent predictor for OS in multivariate analysis (HR 1.45, 95% CI 1.12-1.86; p = 0.004).

Conclusion: The GLR can be a valuable prognostic marker for glucose metabolism and systemic inflammatory status in this patient population. Our research highlights the potential prognostic value of GLR in patients with mRCC receiving TKIs, indicating its potential as a useful tool for clinical decision-making.

Background: The benefit of treatment with tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR-TKI) for lung adenocarcinoma (ADC), stratified by ethnicity, has not yet been fully elucidated.

Methods: We searched PubMed, Embase, and Cochrane databases for studies that investigated EGFR-TKI for lung ADC. We computed hazard ratios (HRs) or risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I² statistics. R, version 4.2.3, was used for statistical analyses.

Results: A total of 18 studies, comprising 4,497 patients with lung ADC randomized to TKIs or chemotherapy alone. TKIs significantly improved OS (HR 0.91; 95% CI 0.88-0.95), PFS (HR 0.60; 95% CI 0.38-0.97), and ORR (HR 0.34; 95% CI 0.25-0.48) in Asian patients, compared with the chemotherapy alone. In Caucasian patients, TKIs significantly improved PFS compared with chemotherapy alone (HR 0.34; 95% CI 0.25-0.48) and ORR(RR 2.35; 95% CI: 1.05-5.28). TKIs significantly reduced any adverse events of any grade in patients with mixed ethnicity (RR 0.86; 95% CI 0.76-0.98) and any adverse events of grade ≥ 3 in Caucasian patients (RR 0.67; 95% CI 0.51-0.89).

Conclusions: This is the first meta-analysis to reveal the ethnic influence on the outcomes of oncologic treatments for patients with lung ADC. In collaboration with in-depth molecular characterization, these data will allow the creation of a clinical-pathological predictive model to increase the magnitude of the expected benefit for patients from different ethnic groups.

Globally, breast and ovarian cancers are major health concerns in women and account for significantly high cancer-related mortality rates. Dysregulations and mutations in genes like TP53, BRCA1/2, KRAS and PTEN increase susceptibility towards cancer. Here, we discuss the impact of mutations in the key regulatory gene, TP53 and polymorphisms in its negative regulator MDM2 which are reported to accelerate cancer progression. Missense mutations, null mutations, transversions, transitions, and point mutations occurring in the TP53 gene can cause an increase in metastatic activity. This review discusses mutations occurring in exon regions of TP53, polymorphisms in MDM2 and their interaction with large ribosomal subunit protein (RPL) leading to cancer development. We also highlight the potential of small molecules e.g. p53 activators like XI-011, Tenovin-1, and Nutlin-3a for the treatment of breast and ovarian cancers. The therapeutic efficacy of natural compounds in amelioration of these two types of cancers is also discussed.

Therapeutic decision-making for older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer highlights the importance of a comprehensive geriatric assessment (CGA). This assessment considers the functional status, comorbidities, and relevant conditions of the patient, and allows for an estimation of life expectancy, but it does not facilitate individualized treatment plans. There are also other challenges to consider related to the cardiac toxicity of the treatments and the under-representation of older patients in clinical trials. The Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica, SEOM), the Spanish Group for Breast Cancer Research (Grupo Español de Investigación en Cáncer de Mama, GEICAM) and the Spanish Group of Study, Treatment and other Experimental Strategies in Solid Tumours (Grupo Español de Estudio, Tratamiento y otras Estrategias Experimentales en Tumores Sólidos, SOLTI) have gathered an expert committee to evaluate the scientific evidence on the management of older patients with HER2-positive breast cancer and to establish recommendations based on a comprehensive review of the existing literature. These recommendations underscore the importance of individualizing treatment plans based on the patient's physical status and tolerability to maximize efficacy while minimizing toxicity. Emphasis is placed on adapting neoadjuvant and adjuvant therapies according to geriatric assessment and specific patient needs. A careful selection of treatment schedules for advanced stages is needed to improve survival and quality of life, assuming that scientific evidence in this age group is limited.

Hereditary polyposis syndromes are significant contributors to colorectal cancer (CRC). These syndromes are characterized by the development of various types and numbers of polyps, distinct inheritance patterns, and extracolonic manifestations. This review explores these syndromes with a focus on their genetic characteristics. Advances in diagnostics, particularly the identification of pathogenic germline variants through massive sequencing technologies, have enhanced our understanding of the genetic alterations associated with polyp formation and CRC risk. Identifying pathogenic variants beyond traditional diagnostic criteria improves the management and surveillance of these syndromes. Genetic diagnosis not only refines patient treatment and surveillance, but also informs relatives of potential risks, enabling appropriate management. However, challenges persist in determining the pathogenicity of newly discovered mutations due to their low prevalence. This review covers hereditary polyposis syndromes, from well-established to newly recognized types, providing insights into their genetic landscapes and highlighting the need for tailored surveillance based on genotype.