Gut Bacteria – Pivotal task in Hematology and Oncology

We have a whole lot of transformation in the field of Hematology/ Oncology these days. Every day new treatments are being tested and developed and we do have advancements targeted on  T cells, immunotherapy, anti-cancer effects, etc. The influence of gut bacteria in body’s immune response is not surprising and not new.

In 2003, Erdman and colleagues, investigating the association between inflammatory bowel disease and colonic malignancy, showed that innate immune dysregulation may provide the link between these two disorders. Specifically, these workers inoculated 129/SvEv Rag2-deficient mice (that were T lymphocyte deficient) and congenic wild-type mice (with normal immune function) with Helicobacter hepaticus or placebo, causing the pathogen-loaded Rag2-deficient mice to develop colitis and, subsequently, colonic cancer. The wild-type mice, with functioning T cells, developed neither condition. To complete their proof, researchers showed that adoptive transfer of regulatory T cells into the Rag2-deficient mice prevented colitis and cancer. Paulos and colleagues showed that total body irradiation, by lowering levels of inhibitory T cells, increased the activity of adoptively transferred CD8-positive lymphocytes. However, this effect was largely vitiated if antibiotics were used to disrupt the gut microflora, and could be reversed by reintroduction of the bacteria or administration of ultra-pure lipopolysaccharides from bacterial cultures, again suggesting an important interplay between microbiome and immune function. Although these observations have clearly been of interest in the efforts to explain the connections between inflammatory bowel disease and subsequent gastrointestinal malignancy, they seem to have taken on a new connotation since the recent therapeutic introduction of immune checkpoint blockade into the active therapeutic management of several malignancies. The concept here is that immune checkpoint blockade releases an attack by T lymphocytes by suppressing the interactions between T-cell inhibitory receptors with their ligands on stromal or tumor cells. One such example is the use of monoclonal antibodies raised against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1). Till date, it has been thought that less than 50% response rate could be due to low antigenicity of tumor cells, low mutational burden, variable expression or distribution of PD-1/PD-L1, aberrations of antigen presentation, or the impact of prior radiotherapy or chemotherapy on the lymphocytes.

Now that, researchers have found an authentic way to transform the donated blood into the universal type which is needed for emergency blood transfusions. These researchers have discovered a way where the enzymes from gut bacteria can efficiently turn type A human blood into type O. Since type O blood type can be donated to anyone as it does not cause any mismatch reaction. The researchers, from the University of British Columbia, say that the clinical trials of the treatment would begin soon. The gut bug enzymes remove markers from the surface of the donor red blood cells present in type A but not in type O. Stripping them away means the recipient’s immune system will think the donor type-A blood is type O and will not attack it for being “foreign”. 

Let us hope for such promising and need of the hour advancements in Medicine in the future too.

For more details, do visit: https://hematology.cmesociety.com/ | https://worldhematology.blogspot.com/

Source: https://www.healio.com/hematology-oncology/practice-management/news/print/hemonc-today/%7Bde32b22b-21af-422b-adde-bc16966af0df%7D/tgif-2018-the-gut-and-immune-function | https://www.bbc.com/news/health-45244770