TRAIL (tumor-necrosis factor related apoptosis-inducing ligand, CD253) and its death receptors TRAIL-R1 and TRAIL-R2 selectively trigger the apoptotic cell death in tumor cells. For that reason, TRAIL has been extensively studied as a target of cancer therapy. In spite of the promising preclinical observations, the TRAIL–based therapies in humans have certain limitations. The two main therapeutic approaches are based on either an administration of TRAIL-receptor (TRAIL-R) agonists or a recombinant TRAIL. These approaches, however, seem to elicit a limited therapeutic efficacy, and only a few drugs have entered the phase II clinical trials. To deliver TRAIL-based therapies with higher anti-tumor potential several novel TRAIL-derivates and modifications have been designed. These novel drugs are, however, mostly preclinical, and many problems continue to be unraveled. We have reviewed the current status of all TRAIL-based monotherapies and combination therapies that have reached phase II and phase III clinical trials in humans. We have also aimed to introduce all novel approaches of TRAIL utilization in cancer treatment and discussed the most promising drugs which are likely to enter clinical trials in humans. To date, different strategies were introduced in order to activate anti-tumor immune responses with the aim of achieving the highest efficacy and minimal toxicity.In this review, we discuss the most promising TRAIL-based clinical trials and their therapeutic strategies.
Our non-randomized study showed that side-to-side LS technique is the preferred method of intrathoracic oesophagogastric anastomosis due to a decreased overall anastomotic leak rate and anastomotic stricture formation compared with HS technique.
In a limited number of human malignancies, anti-CD47 therapy leads to the rapid clearance of tumor cells by macrophages. In esophageal squamous cell carcinoma, anti-CD47 treatment has shown promising results in vitro. However, the CD47 expression pattern in tumor-infiltrating lymphocytes (TILs), which are associated with prolonged overall survival and serve as a positive prognostic factor, is largely unknown. In this study, a total of 36 tissue samples from the tumor, peritumoral tissue, and adjacent healthy esophageal tissue was obtained from 12 esophageal carcinoma (EC) patients, and the surface expression of CD47 was evaluated in natural killer (NK) cells, CD8 + t cells, and the nonlymphocyte cell fraction. We found that the proportions of the evaluated cells and their CD47expressing populations were comparable across the analyzed tissue compartments. However, the proportions of CD47-expressing populations in the analyzed tissue compartments were significantly higher in NK cells and CD8 + T cells than in the nonlymphocyte cell fraction. Importantly, the intensity of CD47 staining was also significantly higher in the tested immune cells than in the nonlymphocyte cell fraction. High expression of CD47 in tissue-infiltrating NK cells and CD8 + t cells in ec patients can, therefore, affect the efficacy of anti-CD47 therapy in EC. CD47 is a widely expressed transmembrane protein of the immunoglobulin superfamily 1. Known as a myeloidspecific immune checkpoint 2 , CD47 has been shown to be involved in multiple T cell functions, regulating either the attenuation or enhancement of T cell responses 3. CD47 interacts with several molecules such as trombospondin 1 (TSP-1), integrins, and signal regulatory proteins γ (SIRPγ) and α (SIRPα) 1. SIRPα is predominantly expressed on macrophages, monocytes, granulocytes, and dendritic cells 4. Its interaction with CD47 induces an inhibitory "don't eat me" signal that prevents cells from phagocytosing CD47-expressing cells 1. CD47 is also expressed in tumor cells in a number of human malignancies 3. CD47 overexpression is associated with a poor prognosis in bladder cancer 5 , breast cancer 6 , and different types of leukemia 7 and is considered to be a marker of cancer recurrence 6. Since CD47 prevents the phagocytosis of tumor cells 1 , CD47 antagonists have been tested in cancer immunotherapy 8. Currently, there are several ongoing phase I clinical trials testing these antagonists for the treatment of solid and hematological malignancies 9,10. An anti-CD47 antibody would presumably increase tumor cell phagocytosis and antitumor CD8 + T cell response priming 11. However, the detailed mechanism underlying the treatment efficacy of anti-CD47 therapy is still unknown. Esophageal carcinoma (EC) remains one of the most lethal human malignancies, with a 5-year survival rate of less than 15% 12. CD47 is overexpressed in the tumor tissues of esophageal squamous cell cancer (ESCC) patients 13,14. In combination with other molecules, CD47, therefore, represents a prognostic factor in ESCC...
Background Textbook outcome has been proposed as a tool for the assessment of oncological surgical care. However, an international assessment in patients undergoing oesophagectomy for oesophageal cancer has not been reported. This study aimed to assess textbook outcome in an international setting. Methods Patients undergoing curative resection for oesophageal cancer were identified from the international Oesophagogastric Anastomosis Audit (OGAA) from April 2018 to December 2018. Textbook outcome was defined as the percentage of patients who underwent a complete tumour resection with at least 15 lymph nodes in the resected specimen and an uneventful postoperative course, without hospital readmission. A multivariable binary logistic regression model was used to identify factors independently associated with textbook outcome, and results are presented as odds ratio (OR) and 95 per cent confidence intervals (95 per cent c.i.). Results Of 2159 patients with oesophageal cancer, 39.7 per cent achieved a textbook outcome. The outcome parameter ‘no major postoperative complication’ had the greatest negative impact on a textbook outcome for patients with oesophageal cancer, compared to other textbook outcome parameters. Multivariable analysis identified male gender and increasing Charlson comorbidity index with a significantly lower likelihood of textbook outcome. Presence of 24-hour on-call rota for oesophageal surgeons (OR 2.05, 95 per cent c.i. 1.30 to 3.22; P = 0.002) and radiology (OR 1.54, 95 per cent c.i. 1.05 to 2.24; P = 0.027), total minimally invasive oesophagectomies (OR 1.63, 95 per cent c.i. 1.27 to 2.08; P < 0.001), and chest anastomosis above azygous (OR 2.17, 95 per cent c.i. 1.58 to 2.98; P < 0.001) were independently associated with a significantly increased likelihood of textbook outcome. Conclusion Textbook outcome is achieved in less than 40 per cent of patients having oesophagectomy for cancer. Improvements in centralization, hospital resources, access to minimal access surgery, and adoption of newer techniques for improving lymph node yield could improve textbook outcome.
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