Blockade of IL1ß and PD1 with Combination Chemotherapy Reduces Systemic Myeloid Suppression in Metastatic Pancreatic Cancer with Heterogeneous Effects in the Tumor.

Innate inflammation promotes tumor development, although the role of innate inflammatory cytokines in established human tumors is unclear. Herein, we report clinical and translational results from a phase Ib trial testing whether IL1ß blockade in human pancreatic cancer would alleviate myeloid immunosuppression and reveal antitumor T-cell responses to PD1 blockade. Patients with treatment-naïve advanced pancreatic ductal adenocarcinoma (n = 10) were treated with canakinumab, a high-affinity monoclonal human antiinterleukin-1ß (IL1ß), the PD1 blocking antibody spartalizumab, and gemcitabine/n(ab)paclitaxel. Analysis of paired peripheral blood from patients in the trial versus patients receiving multiagent chemotherapy showed a modest increase in HLA-DR+CD38+ activated CD8+ T cells and a decrease in circulating monocytic myeloid-derived suppressor cells (MDSC) by flow cytometry for patients in the trial but not in controls. Similarly, we used patient serum to differentiate monocytic MDSCs in vitro and showed that functional inhibition of T-cell proliferation was reduced when using on-treatment serum samples from patients in the trial but not when using serum from patients treated with chemotherapy alone. Within the tumor, we observed few changes in suppressive myeloid-cell populations or activated T cells as assessed by single-cell transcriptional profiling or multiplex immunofluorescence, although increases in CD8+ T cells suggest that improvements in the tumor immune microenvironment might be revealed by a larger study. Overall, the data indicate that exposure to PD1 and IL1ß blockade induced a modest reactivation of peripheral CD8+ T cells and decreased circulating monocytic MDSCs; however, these changes did not lead to similarly uniform alterations in the tumor microenvironment.

Influence of an extreme event-the COVID-19 pandemic-On establishment of and data collection by a citizen science project.

The recent rising incidence of extreme natural events may significantly influence the implementation of citizen science projects, including the success of outreach strategies and the quality and scope of data collection. The MassMammals Watch and subsidiary MassBears citizen science projects, initiated during the height of the pandemic, recruit volunteers to submit sightings of black bears and other mammals. In this study, we evaluated the methods we employed for engaging and retaining community volunteers during a period of intense social restrictions, and we assessed whether such conditions were associated with spatial biases in our collected data. Newspaper features were more likely to recruit volunteers who engaged with the project multiple times, but social media and internet presence were important for reaching a larger audience. Bear sighting submissions peaked in number and were more likely to be in forested areas during 2020, the height of the pandemic, compared to later years, a pattern which we suggest stems from an increased desire to participate in outdoor activities in light of social distancing measures during that year. Such shifts in patterns of data collection are likely to continue, particularly in response to increasing extreme weather events associated with climate change. Here, we both make recommendations on optimal outreach strategies for others initiating citizen science programs and illustrate the importance of assessing potential biases in data collection imposed by extreme circumstances.