macrophage – BioQuakes

Cancer is when abnormal cells divide without control and spread to other parts of the body through the bloodstream and lymph systems to cause illnesses. Immunotherapy is a type of treatment that utilizes a person’s immune system to battle diseases like cancer. Under the branch of immunotherapy, there is a specific therapy that has been recently improved upon.

Chimeric antigen receptor (CAR) T-cell therapy is a treatment that stimulates T-cells to fight cancer by editing them in the lab so they can be released into the body to find and destroy cancer cells. This treatment has been successful in treating certain types of hematologic malignancies but unsuccessful on solid tumors. Hematologic malignancies are cancers that begin in blood-forming tissues such as the bone marrow and in the immune system. Examples of cancers that can be treated with the CAR T-cell therapy include leukemia, lymphoma, and multiple myeloma.

CAR stimulates macrophage phagocytosis function against tumor cells and its immunomodulation capacity. Scientists have already achieved success with this therapy in B cell leukemia/lymphoma but are still caught up on complications with solid tumors. The main challenge about solid tumors arise from its immunosuppressive tumor microenvironment. There is also a limited effect on infiltration into the dense extracellular matrix of the solid tumors.

In this type of therapy, the macrophages are the most important aspect of the success in treatment. Macrophages play a central role in the crosstalk between the adaptive and innate immune system. The immune system defends the body and marks pathogens and cancer cells for macrophages to fight and engulf. The researchers at Zhejiang University partnered with a researcher at the Fujian Medical University and The First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine to study macrophage specific CARs and the development of EGFRvIII (epidermal growth factor receptor variant III) Targeting CAR-iMACs. The chimeric antigen receptors were further genetically engineered into induced pluripotent stem cell (iPSC) derived macrophages (iMACs) so that the CAR treatment was more effective toward solid tumors. The firefly luciferase gene (Ffluc) was discovered to promote the research through the bioluminescence signal response from tumor cells.

Macrophages were equipped with receptors called pattern recognition receptors (PRRs) through the discovery of the importance of bioluminescence cell signaling. The chimeric antigen receptor was then reprogrammed to contain Toll/IL-1R (TIR), a domain containing adapter inducing interferon β. The TIR-containing CAR is a novel engineered PRR that recognizes antigen associated molecular patterns and enables macrophages with antigen dependent polarization to be more pro-inflammatory to aid immune cell therapies in cancer.

Connection to AP Biology:

The chimeric antigen receptor T cell therapy has a great deal of connections to our AP Biology class.

Cancers:

CAR treats certain types of cancers, usually those in the blood-forming tissues. As we learned in AP Bio, cancers form when a cell does not properly divide and bypasses the checkpoints in the mitosis cycle. These abnormal cells don’t always become cancerous but they no longer follow the signals to stop dividing, causing masses that could one day become cancerous.

Macrophages & Phagocytosis:

Macrophages and phagocytosis was something that we learned about in the first semester. Macrophages are specialized cells that are involved in pathogen detection so that phagocytosis can occur and destroy bacteria and other harmful substances.

Phagocytosis occurs when a cell engulfs solid things into the cell. We learned about phagocytosis along with pinocytosis and receptor-mediated endocytosis. In CAR therapy, phagocytosis occurs to engulf pathogens and cancer cells.

Bioluminescence:

In AP Bio, we did not directly learn about bioluminescence but we learned about cell communication and cell signaling. In bacteria, there is quorum sensing and it allows bacteria to share information about cell density and adjust gene expression. In bioluminescence bacteria, the power to produce light is controlled by quorum sensing. One bioluminescent bacteria cannot light up on its own, but when multiple bioluminescent bacteria gather together, quorum sensing signals for the “light” to shine once it senses enough of the bacteria together.

Many salamanders have the special ability to regenerate a lost limb, but adult mammals cannot. The axolotl is a Mexican salamander that is an endangered species in the wild. However, it is unlike most salamanders.

Normally, amphibians, like salamanders and frogs, go through the process of metamorphosis which begins with an egg that hatches into a larvae with gills to live underwater. As they gradually reach the adult stage, salamanders and frogs begin to lose and gain certain traits that allow them to adapt from an aquatic environment to a terrestrial habitat.

Axolotls are adorable creatures that are a special species of salamanders. Instead of going to the process of metamorphosis, they go through the process of paedomorphosis in which they retain their aquatic juvenile state for the rest of their life cycle.

Most salamanders have regenerative abilities but none to the extent of the axolotl. Axolotls can regenerate almost any body part, including the brain, heart, lungs, spinal cord, skin, tail and more. This possibly has to do with their juvenile state. Mammalian embryos and juveniles have the ability to regenerate to some extent, such as the heart tissue and fingertips. However, once mammals reach the adult stage, regeneration just simply isn’t the solution anymore. Mammals being to form a scar at the location of injury.

A team of scientists led by James Godwin, Ph.D., of the Mount Desert Island Biological Laboratory in Bar Harbor, Maine, approached the mystery of molecular regeneration by studying the axolotl, a highly regenerative salamander, versus an adult mouse, a mammal that has limited regenerative ability. In this research, Godwin compared immune cells called macrophages in the axolotl to the macrophages in the mouse to identify the factor that contributed to regeneration. It turns out that the macrophages are crucial to the process of regeneration. When the macrophages were depleted in the axolotl, it formed a scar like mammals do instead of regenerating. Macrophage signalling was similar in both axolotls and mammals when exposed to pathogens such as bacteria, funguses, and viruses. However, when the axolotl was exposed to these pathogens, the signalling promoted new tissue growth while in the mouse, it promoted scarring. Continual research of macrophage signalling in axolotls might one day be able to pull us closer to human regeneration.

In the future, when we need to surgically remove parts of our organs, axolotl regeneration might come in quite handy to regrow our important organs!

This research article relates back to AP Biology because macrophages work together with the its lysosomes to break down foreign pathogens. These macrophages will engulf these invading pathogens into intracellular membrane vesicles through the process of phagocytosis. Once entrapped in the vesicles, the pathogens will be killed with acid.

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: macrophage

Chimeric Antigen Receptor T-Cell Therapy: Successful Research to Improve Cancer Treatments

Regeneration of Lost Limbs in Axolotls

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