Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.

PurposeTumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL).Patients and methodsTavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done.ResultsThe combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses.ConclusionsThe combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors

Spatial and temporal scales of coral reef fish ecological research and management: a systematic map protocol

Background Coral reefs are rapidly changing in response to local and global stressors. Research to better understand and inform the management of these stressors is burgeoning. However, in situ studies of coral reef ecology are constrained by complex logistics and limited resources. Many reef studies are also hampered by the scale-dependent nature of ecological patterns, and inferences made on causal relationships within coral reef systems are limited by the scales of observation. This is because most socio-ecological studies are conducted at scales relevant to the phenomenon of interest. However, management often occurs across a significantly broader, often geopolitical, range of scales. While there is a critical need for incisive coral reef management actions at relevant spatial and temporal scales, it remains unclear to what extent the scales of empirical study overlap with the scales at which management inferences and recommendations are made. This systematic map protocol will evaluate this potential scale mismatch with the goal of raising awareness about the significance of effectively addressing and reporting the scales at which researchers collect data and make assumptions. Methods We will use the Collaboration for Environmental Evidence (CEE) systematic mapping guidelines to identify relevant studies using a framework-based synthesis to summarise the spatial and temporal scales of coral reef fish ecology research and the scales at which management inferences or recommendations are made. Using tested predefined terms, we will search for relevant published academic and grey literature, including bibliographic databases, web-based search engines, and organisational websites. Inclusion criteria for the evidence map are empirical studies that focus on coral reef fish ecological organisation and processes, those informing management interventions and policy decisions, and management documents that cite coral reef research for management decision-making. Study results will be displayed graphically using data matrices and heat maps. This is the first attempt to systematically assess and compare the scales of socio-ecological research conducted on coral reef systems with their management

Research Priorities for Achieving Healthy Marine Ecosystems and Human Communities in a Changing Climate

ABSTRACT: The health of coastal human communities and marine ecosystems are at risk from a host of anthropogenic stressors, in particular, climate change. Because ecological health and human well-being are inextricably connected, effective and positive responses to current risks require multidisciplinary solutions. Yet, the complexity of coupled social-ecological systems has left many potential solutions unidentified or insufficiently explored. The urgent need to achieve positive social and ecological outcomes across local and global scales necessitates rapid and targeted multidisciplinary research to identify solutions that have the greatest chance of promoting benefits for both people and nature. To address these challenges, we conducted a forecasting exercise with a diverse, multidisciplinary team to identify priority research questions needed to promote sustainable and just marine social-ecological systems now and into the future, within the context of climate change and population growth. In contrast to the traditional reactive cycle of science and management, we aimed to generate questions that focus on what we need to know, before we need to know it. Participants were presented with the question, "If we were managing oceans in 2050 and looking back, what research, primary or synthetic, would wish we had invested in today?" We first identified major social and ecological events over the past 60 years that shaped current human relationships with coasts and oceans. We then used a modified Delphi approach to identify nine priority research areas and 46 questions focused on increasing sustainability and well-being in marine social-ecological systems. The research areas we identified include relationships between ecological and human health, access to resources, equity, governance, economics, resilience, and technology. Most questions require increased collaboration across traditionally distinct disciplines and sectors for successful study and implementation. By identifying these questions, we hope to facilitate the discourse, research, and policies needed to rapidly promote healthy marine ecosystems and the human communities that depend upon them

Integrating oceans into climate policy : any green new deal needs a splash of blue

Recent warnings from scientists suggest there is limited time to enact policies to avert wide‐ranging ecological and social damage from climate change. In the United States, discussions about comprehensive national policies to avert climate change have begun, with “Green New Deal” proposals and climate plans put forth by members of Congress and presidential candidates. Oceans are largely absent or separate from these nascent policy proposals. Here, we highlight a policy framework to develop terrestrial and ocean‐integrated policies that can complement and enhance terrestrial‐focused initiatives focused on four specific sectors: 1) energy; 2) transportation; 3) food security; and 4) habitat restoration. Given political friction and constrained budgets, an integrated policy framework offers greater potential to achieve a portfolio of mitigation and adaptation goals in a cost‐effective manner, beyond what could be realized with marine or terrestrial policy solutions alone

Local Responses to Marine Conservation in Zanzibar, Tanzania

Although terrestrial parks and reserves have existed in Tanzania since colonial times, marine protected areas are a much newer endeavor in natural resource conservation. As the importance of marine conservation came to the international forefront in the 1990s, Tanzania experienced a rapid establishment and expansion of marine parks and protected areas. These efforts were crucial to protecting the country’s marine resource base, but they also had significant implications for the lives and fishing patterns of local artisanal fishermen. Terrestrial protected areas in Tanzania have historically been riddled with conflict and local contestation, bringing about numerous debates on the best ways to involve rural residents in conservation planning efforts to establish new “community-based conservation” initiatives. Because marine protected areas do not have the same conflict-ridden history as terrestrial conservation in Tanzania, marine conservation programs present a new opportunity to pilot innovative techniques to involve local communities in protecting and managing their natural resources. The islands of Zanzibar are home to four community-oriented marine protected areas, each of which is sponsored by an external agency, and each of which involves some form of local community component. However, a number of issues arise when working at the community level, requiring nuanced attention to a variety of local factors. The Menai Bay program in southern Zanzibar provides an excellent example of the complexity of factors involved, which can result in dramatically different village-level responses to a single program. These factors include, but are not limited to, differences in geography and infrastructure, the potential for tourism development and alternative sources of income, pre-existing community structures within each village, and the relationship of conservation program managers to the Zanzibari government. While these factors are complex and difficult to predict, it is essential that conservation programs work to take them into account when trying to establish community-based marine conservation programs that will be sustainable in the long term

Local responses to marine conservation in Zanzibar, Tanzania

While terrestrial parks and reserves have existed in Tanzania since colonial times, marine protected areas are a much newer endeavor in natural resource conservation. As the importance of marine conservation came to the international forefront in the 1990s, Tanzania experienced a rapid establishment and expansion of marine parks and protected areas. These efforts were indeed crucial to protecting the country’s marine resource base, but they also had significant implications for the lives and fishing patterns of local artisanal fishermen. Terrestrial protected areas in Tanzania have historically been riddled with conflict and local contestation, bringing about numerous debates on the best ways to involve rural residents in conservation planning efforts to establish new “community-based conservation” programs. However, because marine protected areas do not have the same history as terrestrial conservation in Tanzania, marine conservation programs present a new opportunity to pilot innovative techniques to involve local communities in protecting and managing their natural resources. The islands of Zanzibar are home to four community-oriented marine protected areas, each of which is sponsored by an external agency, and each of which involves some form of local community component. However, a number of issues arise when working at the community level, requiring nuanced attention to a variety of local factors. The Menai Bay program in southern Zanzibar provides an excellent example of the complexity of factors involved, which can result in dramatically different village-level responses to a single program. These factors include, but are not limited to, differences in geography and infrastructure, the potential for tourism development and alternative sources of income, pre-existing community structures within each village, and the relationship of conservation program managers to the Zanzibari government. While these factors are complex and difficult to predict, it is essential that conservation programs take them into account when trying to establish community-based marine conservation programs that will be sustainable in the long-term

Local responses to marine conservation in Zanzibar, Tanzania

While terrestrial parks and reserves have existed in Tanzania since colonial times, marine protected areas are a much newer endeavor in natural resource conservation. As the importance of marine conservation came to the international forefront in the 1990s, Tanzania experienced a rapid establishment and expansion of marine parks and protected areas. These efforts were indeed crucial to protecting the country’s marine resource base, but they also had significant implications for the lives and fishing patterns of local artisanal fishermen. Terrestrial protected areas in Tanzania have historically been riddled with conflict and local contestation, bringing about numerous debates on the best ways to involve rural residents in conservation planning efforts to establish new “community-based conservation” programs. However, because marine protected areas do not have the same history as terrestrial conservation in Tanzania, marine conservation programs present a new opportunity to pilot innovative techniques to involve local communities in protecting and managing their natural resources. The islands of Zanzibar are home to four community-oriented marine protected areas, each of which is sponsored by an external agency, and each of which involves some form of local community component. However, a number of issues arise when working at the community level, requiring nuanced attention to a variety of local factors. The Menai Bay program in southern Zanzibar provides an excellent example of the complexity of factors involved, which can result in dramatically different village-level responses to a single program. These factors include, but are not limited to, differences in geography and infrastructure, the potential for tourism development and alternative sources of income, pre-existing community structures within each village, and the relationship of conservation program managers to the Zanzibari government. While these factors are complex and difficult to predict, it is essential that conservation programs take them into account when trying to establish community-based marine conservation programs that will be sustainable in the long-term