We assess progress toward the protection of 50% of the terrestrial biosphere to address the species-extinction crisis and conserve a global ecological heritage for future generations. Using a map of Earth's 846 terrestrial ecoregions, we show that 98 ecoregions (12%) exceed Half Protected; 313 ecoregions (37%) fall short of Half Protected but have sufficient unaltered habitat remaining to reach the target; and 207 ecoregions (24%) are in peril, where an average of only 4% of natural habitat remains. We propose a Global Deal for Nature—a companion to the Paris Climate Deal—to promote increased habitat protection and restoration, national- and ecoregion-scale conservation strategies, and the empowerment of indigenous peoples to protect their sovereign lands. The goal of such an accord would be to protect half the terrestrial realm by 2050 to halt the extinction crisis while sustaining human livelihoods.

Pembrolizumab's lack of efficacy in TKI naïve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression ≥50%, suggests that it is not an appropriate therapeutic choice in this setting.

Adoptive T-cell therapy can involve donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation, the administration of tumor infiltrating lymphocyte expanded ex-vivo, or more recently the use of T cell receptor or chimeric antigen receptor redirected T cells. However, cellular therapies can pose significant risks, including graft-vs.-host-disease and other on and off-target effects, and therefore strategies need to be implemented to permanently reverse any sign of toxicity. A suicide gene is a genetically encoded molecule that allows selective destruction of adoptively transferred cells. Suicide gene addition to cellular therapeutic products can lead to selective ablation of gene-modified cells, preventing collateral damage to contiguous cells and/or tissues. The “ideal” suicide gene would ensure the safety of gene modified cellular applications by granting irreversible elimination of “all” and “only” the cells responsible for the unwanted toxicity. This review presents the suicide gene safety systems reported to date, with a focus on the state-of-the-art and potential applications regarding two of the most extensively validated suicide genes, including the clinical setting: herpes-simplex-thymidine-kinase and inducible-caspase-9.

Real-time forest monitoring technologies could help track changes in tiger populations.

Purpose Several biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non-small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long term benefit. Experimental Design We assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4 and CD8) and clinical features and outcome in 38 patients with advanced NSCLC treated with pembrolizumab (median follow-up of 4.5 years, range 3.8 to 5.5 years). Results PD-L1 expression and CD8 infiltration correlated with each other and each significantly associated with objective response rate (ORR) and progression free survival (PFS). TMB was independent of PD-L1 and CD8 expression, and trended towards association with ORR and PFS. There was no association between CD4 infiltration and outcomes. Only PD-L1 expression was correlated with overall survival (OS). Among five patients with long-term survival >3 years with no additional systemic therapy, PD-L1 expression was the only discriminating feature. The increased predictive value for PFS and OS of composite biomarker inclusive of PD-L1, CD8, CD4, and TMB was limited. Conclusion In NSCLC patients treated with PD-1 blockade with long term follow up, TMB, PD-L1 and CD8 were each associated with benefit from PD-1 blockade. Pre-treatment PD-L1 expression was correlated with T lymphocyte infiltration as well as OS, while models incorporating TMB and infiltrating CD4 and CD8 lymphocytes did not substantially add to the predictive value of PD-L1 alone for OS.