Press Release: The Body's Built-in Cancer-Fighting System
PHOEBE AHN
No translator
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].
新闻稿：身体内建的抗癌系统
PHOEBE AHN
Jinglan Liang, Zixuan Lin
许多人可能对细胞周期的记忆还停留在初中科学课上：在细胞周期 x中期，染色体（即紧密束缚的DNA）排成一行；在后期，纺锤丝将它们拉开；在末期和胞质分裂阶段，细胞收缩并分裂成两个相同的子细胞。然而，这一细胞分裂过程（有丝分裂）只是细胞生命周期中的一个短暂阶段。细胞在 z的大部分时间都 d处于间期，这一阶段的主要过程是生长，并有两个关键检查点，以确保细胞有足够的资源进入下一阶段，更重要的是检查DNA是否存在错误。正如我们所见，细胞的生命周期受到严格的调控，每个阶段都有特定的功能和预期的目标。然而，“计划赶不上变化”，尽管细胞周期 x设置了诸多保障措施，偶尔也会有错误漏网。如果DNA序列中出现错误，可能会影响细胞的生长或死亡功能，导致不受控制的细胞增殖，即我们所称的癌症。找到癌症的治愈方法一直是一个艰难而漫长的过程，因为癌症源于基因物质的随机变化。然而，近年来我们逐渐认识到，人体其实具有自我抗癌的完整机制，但关键的免疫细胞——单核细胞和巨噬细胞——成为了 c阻碍了我们清除癌细胞的阻碍 d。2023年10月出版于 z的《年轻研究者杂志》上 s的一篇综述论文分析了单核细胞和巨噬细胞如何影响肿瘤细胞的生长，以及我们该 g如何应对这一挑战。
人体的免疫系统可以被比作一个狙击手，通过“癌症免疫循环”识别并摧毁目标癌细胞。该过程的成功依赖于一种特殊的白细胞——细胞毒性T细胞。这些T细胞在肿瘤微环境（TME）中充当“间谍”，利用其T细胞受体收集关于肿瘤细胞膜的信息。凭借这些信息，T细胞能够分泌细胞毒性酶以攻击肿瘤细胞。在理想情况下，这一过程可以让身体区分 q区别癌细胞与健康细胞，从而避免癌症成为当前的全球难题。然而，主要的障碍反而源于我们自身的免疫系统。该综述指出了影响这一肿瘤清除过程的因素——单核细胞和巨噬细胞——以及它们在生化层面上如何干扰肿瘤细胞的生长。
单核细胞和巨噬细胞是免疫系统中的髓系细胞，特别是在肿瘤微环境中十分丰富。单核细胞主要存在于骨髓中，当某一部位显示出炎症迹象时，它们会迅速前往肿瘤微环境。它们会分泌一种称为细胞因子的微小蛋白质，“这类分子用于与其他细胞沟通，从而影响肿瘤微环境中免疫细胞的功能。”细胞因子不仅仅是简单的信号分子，它们更激活了一种促炎症反应，吸引其他可以出入肿瘤微环境的细胞类型，从而削弱了激活关键细胞毒性T细胞的能力。单核细胞还可以分化成另一种免疫细胞——巨噬细胞。在健康的机体中，巨噬细胞在抗击疾病方面发挥重要作用，因为它们“可以吞噬、消化并在膜上展示残余物”，相当于一种高效的“吸尘器”，用于清除细菌、病毒和病变细胞或细胞碎片。然而，巨噬细胞也会分泌细胞因子，进一步加强炎症反应。此外，最近的研究显示，来自肿瘤微环境的巨噬细胞可以迁移到非癌性淋巴结，这表明它们可能在癌组织的扩散中发挥一定作用。
总体而言，尽管我们对这一领域的理解在不断深化，我们仍需开展大量研究 w大量研究仍需开展。该综述探讨的一个潜在方向是“检查点抑制免疫疗法“， 此领域的一些研究已取得积极成果，甚至因此获得了2018年诺贝尔生理学或医学奖。这种免疫疗法的核心在于防止细胞毒性T细胞的“衰竭”，并通过阻断干扰性免疫细胞（如单核细胞和巨噬细胞）上某些蛋白（如PD1、PDL1和CTLA-4）的功能来降低其免疫反应性。尽管该领域仍在进一步研究中，许多肿瘤学专家和临床医生对检查点抑制疗法能够 n替代传统化疗持乐观态度。
参考
- 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].