With a background in both immunology and cancer biology, I’ve always had a fascination with the interplay between the body’s immune system and any tumors that might pop up. Originally, it made sense that the immune system would actively seek out and destroy cancerous cells, but the emerging consensus is that the interactions between cancers and host immunity is far more complex. In addition to growing new blood vessels and reprogramming metabolic processes, there appears to be some imbalance between avoiding immune cells while also promoting tumor-infiltrating inflammatory cells to promote its growth. 1 (Figure 1) Trying to dissect this apparent contradictory relationship between tumors and host immunity remains a hot topic.
Anyone who is remotely interested in biology, or has perhaps scrolled through fitness websites to get in shape, has come across the word "protein". There is, however, much more to proteins than simply being a key player in maintaining active lifestyles. Proteins are ubiquitous in the cells of the body and are the driving force for key cellular processes. In order for proteins to carry out their duties, they need to be well-armed to execute their functions. This process of making the protein competent is achieved through specific post translational modifications (PTMs). The star of the PTMs is a cellular process called phosphorylation. The conventional methods adopted for quantifying phosphorylation are highly labor intensive. The development of phospho-specific antibodies has allowed for a huge sigh of relief from researchers due to their reputation of being quick, and detecting only phosphorylated forms of proteins in a complex mixture of phosphorylated and non-phosphorylated forms.
As we’ve seen over these past few months, a SARS-CoV-2 infection can result in widely different manifestations and severities in the subsequent course of the disease it causes, COVID-19. Many of those infected by SARS-CoV-2 experience a mild to severe illness, with symptoms that include fever, shortness of breath, cough, and fatigue that appear roughly 2-14 days after exposure to the virus. On the other hand, some individuals infected with the virus will remain asymptomatic.
A healthy immune system requires a series of checkpoints to ensure self tolerance and prevent damage to other tissues during immune response. Binding of costimulatory signal transduction molecules (such as CD28, ICOS, GITR) on T cells to their receptors (such as CD80/CD86, ICOSL, GITRL) on antigen presenting cells (APCs) may contribute to T cell activation. However, in some states, inhibitory signals of T cell activation and response occur during the involvement of T cell receptors. These signals are generated by proteins involved in immune checkpoints (eg, PD-1, CTLA-4, TIM-3, and LAG3). Usually PD-1 and CTLA-4 immunological checkpoint proteins are upregulated in T cells infiltrating tumors and bind to their respective ligands, PD-L1 (ligand B7-H1)/PD-L2 (ligand B7- DC) and CD80/86, and down-regulate T cell responses. Immunological checkpoint ligands are often upregulated in cancer cells as a means of evading immune detection. Therefore, immunotherapy by blocking immunological checkpoint protein activation of anti-tumor immunity has become a popular research subject for cancer therapy.
Cluster of differentiation, or CD molecules, are cell surface markers that are used for identification of cell types in pathology and other bioscience disciplines. The expression levels of CD markers may increase or decrease (or disappear altogether, at least to undetectable levels) when cells (for example, leukocytes, red blood cells, platelets, and vascular endothelial cells, etc.) differentiate into new and different lineages. Depending on the CD marker, the expression level may identify a phenotype for different segments of cells, such as when they become active or diseased. Most CD molecules are transmembrane proteins or glycoproteins, including extracellular regions that bind a ligand or opposing receptor, transmembrane regions to anchor the CD marker into the cell, and cytoplasmic regions that may confer some adaptor or catalytic function. Some CD molecules can also be "anchored" on the cell membrane by means of inositol phospholipids. A few CD molecules are carbohydrate haptens. The study of CD molecules can be used in many basic immunology research fields, such as the relationship between CD antigen structure and function, cell activation pathway, signal transduction and cell differentiation, etc. It can be used clinically for disease mechanism research, clinical diagnosis, disease prognosis, efficacy tracking and treatment, and more. CD molecules such as CD4, CD8, CD25, etc. can be used to identify populations of cells when studying samples by flow cytometry or immunofluorescence.