Clinical & Translational Oncology最新文献

This review aims to summarize recent studies and findings within adoptive cell therapies, including tumor-infiltrating lymphocytes, genetically engineered T cell receptors, and chimeric antigen receptor T cells, in the treatment of thoracic malignancies, including non-small cell lung cancer, small cell lung cancer, and malignant pleural mesothelioma. Several trials are ongoing, and a few have reported results, suggesting that adoptive cell therapies may represent a potential treatment option for these patients, especially when checkpoint inhibition has failed. We also discuss the potential implementation of these therapies, as they present a new toxicity profile and an intrinsic financial burden. Despite the challenges to overcome, such as the accurate identification of antigens and developing strategies to improve efficacy and toxicity profiles, new cellular therapies are experiencing significant development in the field of thoracic malignancies.

Programmed Death Protein-1 (PD-1) is a cell surface receptor that serves as a checkpoint for T cells, playing a pivotal role in regulating T-cell apoptosis. The binding of PD-1 to its ligand, Programmed Death Ligand 1 (PD-L1), inhibits anti-tumor immunity by suppressing T-cell activation signals. Indeed, the PD-1/PD-L1 pathway governs the induction and maintenance of immune tolerance within the tumor microenvironment. Consequently, the regulation of PD-1/PD-L1 immune checkpoint expression is of paramount importance. This review summarizes the mechanisms governing PD1/PD-L1 expression at various stages, including transcription, post-transcription (mRNA processing), and post-translation (protein modifications), as well as immunotherapy targeting PD1/PD-L1, aiming to further explore novel strategies for tumor immunotherapy.

Epithelial-to-mesenchymal transition (EMT) is a biological process by which epithelial cells increase their motility and acquire invasive capacity. It represents a crucial driver of cancer metastasis and peritoneal dissemination. EMT plasticity, with cells exhibiting hybrid epithelial/mesenchymal states, and its reverse process, mesenchymal-to-epithelial transition (MET), allows them to adapt to different microenvironments and evade therapeutic intervention. Resistance to conventional treatments, including chemotherapy, is a major problem. Therapies targeting EMT may inhibit tumour cell migration and invasion, while affecting normal cells and repair mechanisms, resulting in potential side effects. This paper addresses the question of the impact of EMT status on cancers with potential spread to the peritoneum, which has remained unclear in literature. Relevant studies were selected from 2000 to 2024. Three macrosections were analysed: (i) pathological characteristics, (ii) surgical implications and (iii) oncological therapies. The focus was on survival and peritoneal recurrence time in patients who underwent surgical treatment.

Background: Small extracellular vesicles (sEV) released by tumor cells (tumor-derived sEV; TEX) mediate intercellular communication between tumor and non-malignant cells and were shown to impact disease progression. This study investigates the relationship between the expression levels of the vesiculation-related genes linked to sEV production and the tumor microenvironment (TME).

Methods: Two independent gene sets were analyzed, both previously linked to sEV production in various non-malignant or malignant cells. Expression profiles were compared among 28 tumor types listed in the Cancer Genome Atlas (TCGA). Gene expression and survival analysis (GEPIA2), immunogenomic analysis (TISIDB), and genomic analysis (GSCA) were performed.

Results: Vesiculation-related genes were overexpressed in tissues of most tumor types compared to healthy tissues, and high expression levels were associated with worse overall survival in cervical squamous cell carcinoma, kidney chromophobe, lower grade glioma, hepatocellular carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma but with improved overall survival in kidney renal clear cell carcinoma. Expression of these signatures correlated with an increased abundance of infiltrating CD4( +) T cells and dendritic cells, a decreased abundance of B cells and eosinophils, and activation of tumor cell apoptosis and epithelial-mesenchymal transition pathways in all tumor types. 17-AAG was identified as a potential drug candidate to target tumors with elevated expression of vesiculation-related genes.

Conclusions: Vesiculation-related genes were associated with distinct immunological and genomic landscapes further emphasizing the important role of TEX in cancer progression.

Introduction: Diagnosing and managing biochemical recurrence (BCR) of prostate cancer (PCa) following primary radical treatment remain a challenge. Implementing next-generation imaging (NGI) techniques has improved metastases detection. However, access to these techniques is heterogeneous, and controversies surround their use and subsequent treatment decisions. In November 2023, a multidisciplinary expert meeting was organized to discuss these aspects. This information was further reviewed in November 2024.

Areas covered: NGI-specific tracers' selection, evidence supporting patient selection for NGI after BRC, current treatment strategies in patients with BRC, and the role of NGIs in current and future therapeutic approaches.

Expert opinion: Despite improved detection performance compared to conventional imaging techniques, the application of NGIs to treatment decision-making and the impact on patient outcomes are yet to be proven. Given the lack of guidance, opinions and recommendations from multidisciplinary expert panels are valuable for diagnosing and adequately treating patients with BRC after radical treatment.

Purpose: This study aimed to further evaluate the potential value of Pan-Immune-Inflammation Value (PIV) as a prognostic marker in patients with laryngeal and pharyngeal tumors.

Methods: A total of 545 patients with laryngeal and pharyngeal tumors who underwent surgery at Qilu Hospital of Shandong University were included. We determined the optimal cutoff of PIV and divided the patients into two groups. The relationship between PIV and clinicopathological features was explored by the chi-square test and the Mann-Whitney U test. Survival analysis and Cox regression analysis were used to evaluate the relationship between PIV and overall survival (OS) and disease-free survival (DFS). We also compared the prognostic predictive value of PIV with other inflammation-related markers. Finally, we developed a simple scoring prediction model based on several independent prognostic parameters.

Results: We found that PIV was statistically associated with clinicopathological features such as tumor stage (p < 0.001), node stage (p = 0.001), postoperative chemotherapy (p = 0.026), and vascular thrombosis (p = 0.027). Survival analysis demonstrated a significant correlation between elevated PIV and reduced OS and DFS (p < 0.0001). Multivariate Cox regression analysis further confirmed PIV as a prognostic indicator (HR 2.507; 95% CI 1.343-4.681; p = 0.004), which is superior to SII, NLR, MLR and PLR. Three of the independent prognostic factors screened by multivariate Cox regression analysis were selected to be used to create a scoring system with a concordance index of 0.756.

Conclusions: Elevated PIV is associated with poor prognosis in patients with laryngeal and pharyngeal tumors, suggesting that PIV may be an important adjunctive indicator for assessing patient prognosis.

Registration information: Registration number: KYLL-202307-001, date: July 2023.

Breast cancer (BC) is one of the most diagnosed cancers in women. Based on histological characteristics, they are classified as non-invasive, or in situ (tumors located within the milk ducts or milk lobules) and invasive. BC may develop from in situ carcinomas over time. Determining prognosis and predicting response to treatment are essential tools to manage this disease and reduce its incidence and mortality, as well as to promote personalized therapy for patients. However, over half of the cases are not associated with known risk factors. In addition, some patients develop resistance to treatment and relapse. Therefore, it is necessary to identify new biomarkers and treatment strategies that improve existing therapies. In this regard, the role of the microbiome is being researched as it could play a role in carcinogenesis and the efficacy of BC therapies. This review aims to describe specific microbiome patterns associated with BC. For this, a literature search was carried out in PubMed database using the MeSH terms "Breast Neoplasms" and "Gastrointestinal Microbiome", including 29 publications. Most of the studies have focused on characterizing the gut or breast tissue microbiome of the patients. Likewise, studies in animal models and in vitro that investigated the impact of gut microbiota (GM) on BC treatments and the effects of the microbiome on tumor cells were included. Based on the results of the included articles, BC could be associated with an imbalance in the GM. This imbalance varied depending on molecular type, stage and grade of cancer, menopause, menarche, body mass index, and physical activity. However, a specific microbial profile could not be identified as a biomarker. On the other hand, some studies suggest that the GM may influence the efficacy of BC therapies. In addition, some microorganisms and bacterial metabolites could improve the effects of therapies or influence tumor development.

Purpose: Angiosarcoma (AS) is a rare malignancy with considerable heterogeneity seen in its aetiology, anatomical location, and clinicopathological behaviour. Diagnosis is often delayed and prognosis poor. The purpose of this study was to perform a retrospective review of all cases of AS over 10 years at a high-volume regional UK referral centre.

Methods/patients: We reviewed all cases of AS discussed at the sarcoma multidisciplinary meetings of University Hospitals Birmingham NHS Foundation Trust from September 2013 to August 2023. Demographic and clinicopathologic features at diagnosis, approaches to treatment, and outcomes were compared between four AS subtypes.

Results: A total of 130 cases were identified. The median age at diagnosis was 71 years, with the majority being female (78%). The most common AS subtype was radiation-induced AS (RIAS) (n = 72; 55%), followed by primary cutaneous (n = 28; 22%), primary non-cutaneous (n = 25; 19%), and AS secondary to lymphoedema (n = 5; 4%). Metastases were present at diagnosis in 18% of patients. Treatment was with surgery in the majority of patients (71%). The median survival for the cohort was 30 months (95% CI 20-40), although this differed significantly by AS subtype (p < 0.001), ranging from 5 months in primary non-cutaneous AS to 76 months in RIAS.

Conclusion: RIAS is the most common AS subtype, with surgery the only potentially curative treatment modality. Overall prognosis varies significantly by subtype. An international consensus on classification of AS subtypes is required to allow meaningful comparisons across studies and/or a prospective multi-centre registry.

Purpose: Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice.

Methods: /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identification of variables predictive of VTE/AT.

Results: A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no significant differences (p = 0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0-22.9) and the group that did not (median 9.86 months, 95% CI 6.3-13.4). The presence of liver metastases was predictive of VTE/AT (p < 0.05).

Conclusions: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not significantly impact survival. The presence of liver metastases can predict these events.