Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.

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The blockade of immune checkpoints in cancer immunotherapy

https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

/pdf/the-basics-of-epithelial-mesenchymal-transition-xe9crzoewf.pdf

The basics of epithelial-mesenchymal transition

Background Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. Methods In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. Results As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The media...

/pdf/safety-and-activity-of-anti-pd-l1-antibody-in-patients-with-2g1sbl9vc4.pdf

Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

The transdifferentiation of epithelial cells into motile mesenchymal cells, a process known as epithelial-mesenchymal transition (EMT), is integral in development, wound healing and stem cell behaviour, and contributes pathologically to fibrosis and cancer progression. This switch in cell differentiation and behaviour is mediated by key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix-loop-helix transcription factors, the functions of which are finely regulated at the transcriptional, translational and post-translational levels. The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues. Among these, transforming growth factor-β (TGFβ) family signalling has a predominant role; however, the convergence of signalling pathways is essential for EMT.

Molecular mechanisms of epithelial–mesenchymal transition

Changes in Plasma Levels of VEGF-C and Endothelin-1 During the First Post-Transplant Year Are Predictive of Cardiac Allograft Vasculopathy: Results From the CTOT-05 Study.: Abstract# A23

Transplant‐related complications

Low Nephron Number: Initial "Hit" in Adult Hypertension and Renal Disease

INDUCTION OF MIXED HEMATOPOIETIC CHIMERISM AND TOLERANCE WITH SUBOPTIMAL RECIPIENT T CELL DEPLETION, 3GY TBI AND ANTI-CD154 OR CTLA4Ig: TOWARD A CLINICAL REGIMEN USEFUL FOR CADAVERIC DONORS

1In the early 1980s, before the renoprotective effects of ACE inhibitors were apparent, renal failure in diabetic patients would occur within 5-10 years following the onset of persistent proteinuria. 2-4 Today, the evidence suggests that strategies for retarding the development of diabetic nephropathy must employ a multifactoral approach. Agents that directly block the renin-angiotensin system (RAS) have been shown to decrease proteinuria and reduce the annual rate of decline in the glomerular filtration rate (GFR) to targets <0.5 gm/day and 2 mL/min. In addition, effective therapy involves lowering blood pressure, dietary protein and salt restriction, glycemic control, lipid lowering, use of antiplatelet agents, correction of elevated Ca 2+ xP product, treatment

Anil Chandraker

Papers

Changes in Plasma Levels of VEGF-C and Endothelin-1 During the First Post-Transplant Year Are Predictive of Cardiac Allograft Vasculopathy: Results From the CTOT-05 Study.: Abstract# A23

Transplant‐related complications

Low Nephron Number: Initial "Hit" in Adult Hypertension and Renal Disease

INDUCTION OF MIXED HEMATOPOIETIC CHIMERISM AND TOLERANCE WITH SUBOPTIMAL RECIPIENT T CELL DEPLETION, 3GY TBI AND ANTI-CD154 OR CTLA4Ig: TOWARD A CLINICAL REGIMEN USEFUL FOR CADAVERIC DONORS

Attaining Renoprotection by Targeting the Renin-Angiotensin System