Does time since fire drive live aboveground biomass and stand structure in low fire activity boreal forests? Impacts on their management.

Boreal forests subject to low fire activity are complex ecosystems in terms of structure and dynamics. They have a high ecological value as they contain important proportions of old forests that play a crucial role in preserving biodiversity and ecological functions. They also sequester important amounts of carbon at the landscape level. However, the role of time since fire in controlling the different processes and attributes of those forests is still poorly understood. The Romaine River area experiences a fire regime characterized by very rare but large fires and has recently been opened to economic development for energy and timber production. In this study, we aimed to characterize this region in terms of live aboveground biomass, merchantable volume, stand structure and composition, and to establish relations between these attributes and the time since the last fire. Mean live aboveground biomass and merchantable volume showed values similar to those of commercial boreal coniferous forests. They were both found to increase up to around 150 years after a fire before declining. However, no significant relation was found between time since fire and stand structure and composition. Instead, they seemed to mostly depend on stand productivity and non-fire disturbances. At the landscape level, this region contains large amounts of biomass and carbon stored resulting from the long fire cycles it experiences. Although in terms of merchantable volume these forests seemed profitable for the forest industry, a large proportion were old forests or presented structures of old forests. Therefore, if forest management was to be undertaken in this region, particular attention should be given to these old forests in order to protect biodiversity and ecological functions. Partial cutting with variable levels of retention would be an appropriate management strategy as it reproduces the structural complexity of old forests.

Negative impacts of high temperatures on growth of black spruce forests intensify with the anticipated climate warming.

An increasing number of studies conclude that water limitations and heat stress may hinder the capacity of black spruce (Picea mariana (Mill.) B.S.P.) trees, a dominant species of Canada's boreal forests, to grow and assimilate atmospheric carbon. However, there is currently no scientific consensus on the future of these forests over the next century in the context of widespread climate warming. The large spatial extent of black spruce forests across the Canadian boreal forest and associated variability in climate, demography, and site conditions pose challenges for projecting future climate change responses. Here we provide an evaluation of the impacts of climate warming and drying, as well as increasing [CO2 ], on the aboveground productivity of black spruce forests across Canada south of 60°N for the period 1971 to 2100. We use a new extensive network of tree-ring data obtained from Canada's National Forest Inventory, spatially explicit simulations of net primary productivity (NPP) and its drivers, and multivariate statistical modeling. We found that soil water availability is a significant driver of black spruce interannual variability in productivity across broad areas of the western to eastern Canadian boreal forest. Interannual variability in productivity was also found to be driven by autotrophic respiration in the warmest regions. In most regions, the impacts of soil water availability and respiration on interannual variability in productivity occurred during the phase of carbohydrate accumulation the year preceding tree-ring formation. Results from projections suggest an increase in the importance of soil water availability and respiration as limiting factors on NPP over the next century due to warming, but this response may vary to the extent that other factors such as carbon dioxide fertilization, and respiration acclimation to high temperature, contribute to dampening these limitations.

Heterologous prime-boost cellular vaccination induces potent antitumor immunity against triple negative breast cancer.

Introduction: Triple negative breast cancer (TNBC) is the most aggressive and hard-to-treat subtype of breast cancer, affecting 10-20% of all women diagnosed with breast cancer. Surgery, chemotherapy and hormone/Her2 targeted therapies are the cornerstones of treatment for breast cancer, but women with TNBC do not benefit from these treatments. Although the prognosis is dismal, immunotherapies hold significant promise in TNBC, even in wide spread disease because TNBC is infiltrated with more immune cells. This preclinical study is proposing to optimize an oncolytic virus-infected cell vaccine (ICV) based on a prime-boost vaccination strategy to address this unmet clinical need. Methods: We used various classes of immunomodulators to improve the immunogenicity of whole tumor cells in the prime vaccine, followed by their infection with oncolytic Vesicular Stomatitis Virus (VSVd51) to deliver the boost vaccine. For in vivo studies, we compared the efficacy of a homologous prime-boost vaccination regimen to a heterologous strategy by treating 4T1 tumor bearing BALB/c mice and further by conducting re-challenge studies to evaluate immune memory responses in surviving mice. Due to the aggressive nature of 4T1 tumor spread (akin to stage IV TNBC in human patients), we also compared early surgical resection of primary tumors versus later surgical resection combined with vaccination. Results: In vitro results demonstrated that immunogenic cell death (ICD) markers and pro-inflammatory cytokines were released at the highest levels following treatment of mouse 4T1 TNBC cells with oxaliplatin chemotherapy and influenza vaccine. These ICD inducers also contributed towards higher dendritic cell recruitment and activation. With the top ICD inducers at hand, we observed that treatment of TNBC-bearing mice with the influenza virus-modified prime vaccine followed by VSVd51 infected boost vaccine resulted in the best survival. Furthermore, higher frequencies of both effector and central memory T cells along with a complete absence of recurrent tumors were observed in re-challenged mice. Importantly, early surgical resection combined with prime-boost vaccination led to improved overall survival in mice. Conclusion: Taken together, this novel cancer vaccination strategy following early surgical resection could be a promising therapeutic avenue for TNBC patients.

Remodeling the tumor immune microenvironment with oncolytic viruses expressing miRNAs.

MiRNAs (miRNA, miR) play important functions in the tumor microenvironment (TME) by silencing gene expression through RNA interference. They are involved in regulating both tumor progression and tumor suppression. The pathways involved in miRNA processing and the miRNAs themselves are dysregulated in cancer. Consequently, they have become attractive therapeutic targets as underscored by the plethora of miRNA-based therapies currently in pre-clinical and clinical studies. It has been shown that miRNAs can be used to improve oncolytic viruses (OVs) and enable superior viral oncolysis, tumor suppression and immune modulation. In these cases, miRNAs are empirically selected to improve viral oncolysis, which translates into decreased tumor growth in multiple murine models. While this infectious process is critical to OV therapy, optimal immunomodulation is crucial for the establishment of a targeted and durable effect, resulting in cancer eradication. Through numerous mechanisms, OVs elicit a strong antitumor immune response that can also be further improved by miRNAs. They are known to regulate components of the immune TME and promote effector functions, antigen presentation, phenotypical polarization, and varying levels of immunosuppression. Reciprocally, OVs have the power to overcome the limitations encountered in canonical miRNA-based therapies. They deliver therapeutic payloads directly into the TME and facilitate their amplification through selective tumoral tropism and abundant viral replication. This way, off-target effects can be minimized. This review will explore the ways in which miRNAs can synergistically enhance OV immunotherapy to provide the basis for future therapeutics based on this versatile combination platform.