Cancer immunotherapy is an evolving field of research. Cytokines have been conceptualized as an anticancer therapy for longer than most other cancer immunotherapy modalities. Yet, to date, only two cytokines are FDA-approved: IFN-α and IL-2. Despite the initial breakthrough, both agents have been superseded by other, more efficacious agents such as immune checkpoint inhibitors. Several issues persist with cytokine-based cancer therapies; these are broadly categorised into a) high toxicity and b) low efficacy. Despite the only moderate benefits with early cytokine-based cancer therapies, advances in molecular engineering, genomics, and molecular analysis hold promise to optimise and reinstate cytokine-based therapies in future clinical practice. This review considers five important concepts for the successful clinical application of cytokine-based cancer therapies including: (i) improving pharmacokinetics and pharmacodynamics, (ii) improving local administration strategies, (iii) understanding context-dependent interactions in the tumour-microenvironment, (iv) elucidating the role of genetic polymorphisms, and (v) optimising combination therapies. IL-10 has been the focus of attention in recent years and is discussed herein as an example.IL-10 is a pleiotropic cytokine with anti-inflammatory and immunostimulatory functions. In cancer, IL-10 may exert pro-or anti-tumour effects (4). Early research aimed to 3247 This article is freely accessible online.
Cytokines are soluble proteins that mediate intercellular signaling regulating immune and inflammatory responses. Cytokine modulation represents a promising cancer immunotherapy approach for immune-mediated tumor regression. However, redundancy in cytokine signaling and cytokines' pleiotropy, narrow therapeutic window, systemic toxicity, short half-life and limited efficacy represent outstanding challenges for cytokine-based cancer immunotherapies. Recently, there has been interest in the paradoxical role of IL-10 in cancer, its controversial prognostic utility and novel strategies to enhance its therapeutic profile. Here, the authors review the literature surrounding the role of IL-10 within the tumor microenvironment, its prognostic correlates to cancer patient outcomes and its pro- and antitumor effects, and they assess the legitimacy of potential therapeutic strategies harnessing IL-10 by outlining the notable preclinical and clinical evidence to date.
AimsFunctional Neurological Disorder (FND) is known to be associated with high healthcare resource utilisation and poor quality of life. Patients’ understanding of the disorder is considered instrumental in improving prognosis.We produced a symptom self-management patient education strategy with a booklet and FND symptoms recording template in a community neuropsychiatry setting. We embedded this psychoeducation intervention in a post-nursing triage model of care.MethodA co-production cycle of patient education material was implemented as part of a Quality Improvement Project (QIP) at East Kent Neuropsychiatry Service. Year 4 medical students completed their first QIP cycle involving 4 students, 2 multidisciplinary team members and 4 patients with functional neurological presentations. An FND leaflet and symptom recording template was produced and reviewed using feedback domains such as leaflet readability, perceived usefulness, and template design. The revised version of leaflet was then pilot-tested in second QIP cycle via email or post to 12 patients awaiting their group psychology or neuropsychiatry appointments for treatment of FND. The uptake and impact of leaflet was assessed using telephone-based structured feedback collection.ResultThe first QIP cycle included 10 participants and generated qualitative knowledge domains, providing examples of different types of FND presentations and a biological-psychological-social model explaining onset and/or recurrence of FND symptoms. Group patient feedback and co-production input allowed inclusion of the patient voice and a re-design of leaflet and symptom recording template.The second QIP cycle involved 12 participants: feedback was collected two weeks after circulation of patient education material. Only 5 participants (42%) had read and used their education leaflet and template during this period. Patients described the booklet as useful overall, but thought it to be more useful at the point of diagnosis and referral to neuropsychiatry. Qualitatively, patients wished there to be more emphasis on FND being explained as “less psychiatric, more a neuropsychiatric problem”, and that it would be “very good for someone who had just been diagnosed”. 80% of responders rated the leaflet quality 8/10 or above. These respondents felt that the leaflet had helped them understand their condition better than they did previously. Usefulness of an additional self-formulation flowchart was rated as 8/10 or below by all patients - with several finding it difficult to use.ConclusionOur QIP supports the need for early patient education when discussing diagnosis of FND. The finding of 42% uptake within two weeks of leaflet dispatch is encouraging.
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