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 Despite the initial breakthrough, both agents have been superseded by other, more efficacious agents such as immune checkpoint inhibitors.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.

Purpose: There is a growing emphasis placed on self-directed learning (SDL) within medical education. Yet, little is known about the SDL resources medical students are using. This study aimed to identify patterns in medical students’ SDL behaviours, their SDL resource choices, factors motivating these choices, and the potential impact of the COVID-19 pandemic on these variables.MethodsA online cross-sectional survey comprised of multiple choice, ranked, and free text response questions was disseminated to medical students across all 41 UK medical schools between April and July 2020. Comparison of independent study hours and sources of study materials prior to and during the COVID-19 pandemic was undertaken. Motivational factors guiding resource choices and awareness of Free Open Access Meducation (FOAM) was also investigated. ResultsA target sample size of 75 per medical school across a total of 41 medical schools within the UK were targeted (3075 total students). 1564 responses were included for analysis. University-provided information comprised the most commonly used component of independent study time, but a minority of total independent study time. Independent study time increased as a result of the COVID-19 pandemic (P<0.001). All sub-cohorts except males reported a significant increase in the use of resources such as free websites and question banks (P<0.05) and paid websites (P<0.05) as a result of the pandemic. Accessibility was the most influential factor guiding resource choice (Friedman’s μrank=3.97, p<0.001). ConclusionThere is a growing trend towards an increase in the use of learning resources independent of university provision. Educators must ensure equitable access to such materials whilst supporting students in making informed choices regarding their independent study behaviours.

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