30 research outputs found
Long Overall Survival After Dendritic Cell Vaccination in Metastatic Uveal Melanoma Patients
Purpose: To assess the safety and efficacy of dendritic cell vaccination in metastatic uveal melanoma. Design: Interventional case series. Methods: We analyzed 14 patients with metastatic uveal melanoma treated with dendritic cell vaccination. Patients with metastatic uveal melanoma received at least 3 vaccinations with autologous dendritic cells, professional antigen-presenting cells loaded with melanoma antigens gp100 and tyrosinase. The main outcome measures were safety, immunologic response, and overall survival. Results: Tumor-specific immune responses were induced with dendritic cell vaccination in 4 (29%) of14 patients. Dendritic cell-vaccinated patients showed a median overall survival with metastatic disease of 19.2months, relatively long compared with that reported in the literature. No severe treatment-related toxicities (common toxicity criteria grade 3 or 4) were observed. Conclusions: Dendritic cell vaccination is feasible and safe in metastatic uveal melanoma. Dendritic cell-based immunotherapy is potent to enhance the host's antitumor immunity against uveal melanoma in approximately one third of patients. Compared with other prospective studies with similar inclusion criteria, dendritic cell vaccination may be associated with longer than average overall survival in patients with metastatic uveal melanoma
Case Report: A severe case of immunosuppressant-refractory immune checkpoint inhibitor-mediated colitis rescued by tofacitinib
Immune checkpoint inhibitor therapy for cancer treatment can give rise to a variety of adverse events. Here we report a male patient with metastatic melanoma who experienced life-threatening colitis and duodenitis following treatment with ipilimumab and nivolumab. The patient did not respond to the first three lines of immunosuppressive therapy (corticosteroids, infliximab, and vedolizumab), but recovered well after administration of tofacitinib, a JAK inhibitor. Cellular and transcriptional data on colon and duodenum biopsies shows significant inflammation in the tissue, characterized by a large number of CD8 T cells and high expression of PD-L1. While cellular numbers do decrease during three lines of immunosuppressive therapy, CD8 T cells remain relatively high in the epithelium, along with PD-L1 expression in the involved tissue and expression of colitis-associated genes, indicating an ongoing colitis at that moment. Despite all immunosuppressive treatments, the patient has an ongoing tumor response with no evidence of disease. Tofacitinib might be a good candidate to consider more often for ipilimumab/nivolumab-induced colitis
The clinical application of cancer immunotherapy based on naturally circulating dendritic cells
Dendritic cells (DCs) can initiate and direct adaptive immune responses. This ability is exploitable in DC vaccination
strategies, in which DCs are educated ex vivo to present tumor antigens and are administered into the patient with
the aim to induce a tumor-specific immune response. DC vaccination remains a promising approach with the potential
to further improve cancer immunotherapy with little or no evidence of treatment-limiting toxicity. However, evidence
for objective clinical antitumor activity of DC vaccination is currently limited, hampering the clinical implementation.
One possible explanation for this is that the most commonly used monocyte-derived DCs may not be the best source
for DC-based immunotherapy. The novel approach to use naturally circulating DCs may be an attractive alternative. In
contrast to monocyte-derived DCs, naturally circulating DCs are relatively scarce but do not require extensive culture
periods. Thereby, their functional capabilities are preserved, the reproducibility of clinical applications is increased, and
the cells are not dysfunctional before injection. In human blood, at least three DC subsets can be distinguished,
plasmacytoid DCs, CD141+ and CD1c+ myeloid/conventional DCs, each with distinct functional characteristics. In
completed clinical trials, either CD1c+ myeloid DCs or plasmacytoid DCs were administered and showed encouraging
immunological and clinical outcomes. Currently, also the combination of CD1c+ myeloid and plasmacytoid DCs as well
as the intratumoral use of CD1c+ myeloid DCs is under investigation in the clinic. Isolation and culture strategies for
CD141+ myeloid DCs are being developed. Here, we summarize and discuss recent clinical developments and future
prospects of natural DC-based immunotherapy
The ESSO core curriculum committee update on surgical oncology
Introduction
Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology.
Material and methods
The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts.
Results
The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology.
Conclusions
As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients
Genetic biomarkers in melanoma of the ocular region:What the medical oncologist should know
ASO Author Reflections: Frequent Relapses Prior to the Start of Adjuvant Therapy in Stage IIIB/C Melanoma
The safety risk of information overload and bureaucracy in oncology clinical trial conduct
Performance of clinical trials has led to major therapeutic developments and substantial improvements in the field of medical oncology. To ensure patient's safety, regulatory aspects for proper clinical trial conduct have been increased over the past two decades but seem to cause information overload and ineffective bureaucracy, possibly even impacting patient safety. To put this in perspective, after the implementation of Directive 2001/20/EC in the European Union, a 90 per cent increase in trial launching time, a 25 per cent decrease in patient participation and a 98 per cent rise in administrative trial costs were reported. The time to initiate a clinical trial has increased from a few months to several years in the past three decades. Moreover, there is a serious risk that information overload with relatively unimportant data endangers the decision-making processes and distracts from essential patient safety information. It is now a critical moment in time to improve efficient clinical trial conduct for our future patients diagnosed with cancer. We are convinced that a reduction of the administrative regulations, information overload, and simplification of the procedures for trial conductance may improve patient safety. In this Current Perspective, we give insight in the current regulatory aspects of clinical research, evaluate the practical consequences of these regulations, and propose specific improvements for optimal clinical trial conduct
T-cell Landscape in a Primary Melanoma Predicts the Survival of Patients with Metastatic Disease after Their Treatment with Dendritic Cell Vaccines
Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors
The brain is a specialized immune site representing a unique tumor microenvironment. The availability of fresh brain tumor material for ex vivo analysis is often limited because large parts of many brain tumors are resected using ultrasonic aspiration. We analyzed ultrasonic tumor aspirates as a biosource to study immune suppressive mechanisms in 83 human brain tumors. Lymphocyte infiltrates in brain tumor tissues and ultrasonic aspirates were comparable with respect to lymphocyte content and viability. Applying ultrasonic aspirates, we detected massive infiltration of CD4+FoxP3+CD25high CD127low regulatory T cells (Tregs) in glioblastomas (n = 29) and metastatic brain tumors (n = 20). No Treg accumulation was observed in benign tumors such as meningiomas (n = 10) and pituitary adenomas (n = 5). A significant Treg increase in blood was seen only in patients with metastatic brain tumors. Tregs in high-grade tumors exhibited an activated phenotype as indicated by decreased proliferation and elevated CTLA-4 and FoxP3 expression relative to blood Tregs. Functional analysis showed that the tumor-derived Tregs efficiently suppressed cytokine secretion and proliferation of autologous intratumoral lymphocytes. Most tumor-infiltrating Tregs were localized in close proximity to effector T cells, as visualized by immunohistochemistry. Furthermore, 61% of the malignant brain tumors expressed programmed death ligand-1 (PD-L1), while the inhibitory PD-1 receptor was expressed on CD4+ effector cells present in 26% of tumors. In conclusion, using ultrasonic tumor aspirates as a biosource we identified Tregs and the PD-L1/PD-1 pathway as immune suppressive mechanisms in malignant but not benign human brain tumors