Phoebe Ahn
Many of us may vaguely remember the cell cycle from middle school science class; tight bundles of DNA called chromosomes line up into a row in metaphase, spindle fibers pull them apart in anaphase, and the cell pinches in half to create two identical daughter cells in the final stages of telophase and cytokinesis. However, this process of cell division (mitosis) is just one short period in a cell’s life cycle. Cells spend most of their time in interphase, periods of growth during which two checkpoints occur to ensure the cell has enough resources to continue onto the next stage and, more importantly, check whether the DNA has any mistakes. As we can see, cells have a tightly regulated lifestyle. Each stage has a function with an expected goal that must be met. Yet, “the best-laid plans of mice and men often go awry.” Despite all the safeguards put in place, every now and then, a mistake slips by. If a mistake is made in the DNA sequence, it could lead to an alteration in the function of cell growth or cell death, resulting in uncontrolled cell growth, a condition otherwise known as cancer. The battle with finding a cure for cancer has been long and arduous, given that it is a unique disease arising from a random change in genetic material. However, in recent years we have come to realize that our body has all the machinery needed to fight cancer on its own, but a few key players, monocytes and macrocytes, prevent our body from eradicating cancer cells. The review paper published in the October issue of the Journal of Young Investigators analyzes how the immune cells monocytes and macrophages affect tumor cell growth as well as how we are combating this issue.
The body’s immune system can be compared to a sniper – it identifies target cancer cells and destroys them using a process called the “cancer immunity cycle”. This process’ success relies on a specific type of white blood cell, the cytotoxic T-cell. This T-cell acts as a spy in the tumor microenvironment (TME), gathering intel on tumor cell membranes using their T-cell receptors. Using the information gathered, these cells can irradiate the tumor cells by secreting cytotoxic enzymes. Ideally, this process would allow the body to differentiate between cancerous cells and healthy cells. Thus, cancer would not present such a worldwide problem as it is today. However, the main obstacle that lies in our way ironically comes from our own body. This review identifies interring factors of this tumor-removing process, immune cells called monocytes and macrophages, as well as how they interfere with tumor cell growth on a biochemical level.
Monocytes and macrophages are types of immune myeloid cells particularly abundant in the TME. Monocytes reside in bone marrow and rush to the TME when the site shows signs of inflammation. They secrete small proteins called cytokines, “molecules used to communicate with other cells – thereby affecting immune cells and their functions within the TME.” Rather than just the essential players quickly dealing with the issue, cytokines sound an alarm that results in a proinflammatory response, calling in other cell types that can move in and out of the TME, thus reducing the body’s ability to activate the crucial cytotoxic T-cells. Monocytes can also differentiate or transform into another type of immune cell called a macrophage. Macrophages, in a healthy body, play an important role in fighting diseases as they have the “ability to engulf, digest, and present debris on their membrane.” In other words, they act a bit like a high functioning vacuum cleaner for bacteria, viruses, and generally unhealthy cells or cell debris. However, macrophages also secrete cytokines, contributing to the inflammatory response. Moreover, recent reports have suggested that macrophages from the TME can migrate to non-cancerous lymph nodes, suggesting that they may be partially responsible for the spread of cancerous tissue.
In general, though our understanding has expanded and deepened, the field still requires much research. One possible concept this review explores is checkpoint blockade immunotherapy. Studies have been done on the subject, yielding positive results and even winning the 2018 Nobel Prize in Physiology and Medicine. This type of immunotherapy focuses on preventing T-cell “exhaustion” in cytotoxic T-cells as well as decreasing monocyte and macrophage immune responsiveness by using blocking agents for certain proteins found on these interfering immune cells such as PD1, PDL1, and CTLA-4. This area of research is still under investigation, but many scientists and clinicians in the oncology department are hopeful that checkpoint blockade therapy can provide a different alternative to chemotherapy.
References
McCreery, C. and Zamora, I. (2022) ‘Monocytes and Macrophages in the Cancer Immunity Cycle’, Journal of Young Investigators, 25(9), available: https://www.jyi.org/current-issue-1.
Moeller, C. (2022) ‘BICD 100 Lecture #1’, University of California, San Diego. August 1. [accessed 26 September 2022].