SummaryRegulatory T cells (Tregs) play a pivotal role in maintaining immunological tolerance, but they can also play a detrimental role by preventing antitumor responses. Here, we characterized T helper (Th)-like Treg subsets to further delineate their biological function and tissue distribution, focusing on their possible contribution to disease states. RNA sequencing and functional assays revealed that Th2-like Tregs displayed higher viability and autocrine interleukin-2 (IL-2)-mediated activation than other subsets. Th2-like Tregs were preferentially found in tissues rather than circulation and exhibited the highest migratory capacity toward chemokines enriched at tumor sites. These cellular responses led us to hypothesize that this subset could play a role in maintaining a tumorigenic environment. Concurrently, Th2-like Tregs were enriched specifically in malignant tissues from patients with melanoma and colorectal cancer compared to healthy tissue. Overall, our results suggest that Th2-like Tregs may contribute to a tumorigenic environment due to their increased cell survival, higher migratory capacity, and selective T-effector suppressive ability.
Lymph node metastasis informs prognosis and is a key factor in deciding further management, particularly adjuvant chemotherapy. It is core to all contemporary staging systems, including the widely used tumor node metastasis staging system. Patients with node-negative disease have 5-year survival rates of 70%-80%, implying a significant minority of patients with occult lymph node metastases will succumb to disease recurrence. Enhanced staging techniques may help to identify this subset of patients, who might benefit from further treatment. Obtaining adequate numbers of lymph nodes is essential for accurate staging. Lymph node yields are affected by numerous factors, many inherent to the patient and the tumour, but others related to surgical and histopathological practice. Good lymph node recovery relies on close collaboration between surgeon and pathologist. The optimal extent of surgical resection remains a subject of debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high arterial ligation and complete mesocolic excision are amongst the surgical techniques with plausible oncological bases, but which are not supported by the highest levels of evidence. With further development and refinement, intra-operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to the optimum extent of lymphadenectomy, but in its present form, it is beset by false negatives, skip lesions and failures to identify a sentinel node. Once resected, histopathological assessment of the surgical specimen can be improved by thorough dissection techniques, step-sectioning of tissue blocks and immunohistochemistry. More recently, molecular methods have been employed. In this review, we consider the numerous factors that affect lymph node yields, including the impact of the surgical and histopathological techniques. Potential future strategies, including the use of evolving technologies, are also discussed.
The explosive Zika virus epidemic in the Americas is amplifying spread of this emerging pathogen into previously unaffected regions of the world, including Europe (Gulland, 2016), where local populations are immunologically naïve. As summertime approaches in the northern hemisphere, Aedes mosquitoes in Europe may find suitable climatic conditions to acquire and subsequently transmit Zika virus from viremic travellers to local populations. While Aedes albopictus has proven to be a vector for the transmission of dengue and chikungunya viruses in Europe (Delisle, E., et al., 2015, ECDC,, n.d) there is growing experimental and ecological evidence to suggest that it may also be competent for Zika virus(Chouin-Carneiro et al., 2016; Grard et al., 2014; Li et al., 2012; Wong et al., 2013). Here we analyze and overlay the monthly flows of airline travellers arriving into European cities from Zika affected areas across the Americas, the predicted monthly estimates of the basic reproduction number of Zika virus in areas where Aedes mosquito populations reside in Europe (Aedes aegypti in Madeira, Portugal and Ae. albopictus in continental Europe), and human populations living within areas where mosquito-borne transmission of Zika virus may be possible. We highlight specific geographic areas and timing of risk for Zika virus introduction and possible spread within Europe to inform the efficient use of human disease surveillance, vector surveillance and control, and public education resources.
Real-time elastography in its present form cannot replace transient elastography for noninvasive assessment of liver fibrosis.
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