by Anuli Khairatkar
Cancer is a universally feared condition, but what about it is so terrifying? The danger of cancer lies not just in its origins, but also in how it interacts within the body once it begins to grow. At its core, cancer is the abnormal and uncontrolled growth of cells. While we often think of cancer as a random misfortune, only about 5 to 10 percent of all cases are caused by spontaneous, inherited mutations in our DNA. The vast majority of cases, however, are driven by environmental and lifestyle factors such as diet, smoking, chronic infections, pollution, and long-term stress, which lead to acquired genetic mutations over time. With years of research, we now have a better understanding on how cancer might arise in the first place, however what makes it so difficult to treat remains an unsolved complex question.
As tumors develop, they begin to engage with and exploit our complex biological systems. One of the most critical systems they manipulate is our defense mechanism, the immune system. Typically, the immune system is equipped with various types of immune cells and molecular messengers that work together to detect and eliminate abnormal cells. One special subset of immune cells known as T cells plays a key role in this defense. They scan for “ID badges” on the surface of cells to determine whether they belong to the category of normal cells or not. If a cell is identified as abnormal, T cells spring into action by releasing proteins that trigger the destruction of the cancer cell. To coordinate this defense, the immune system uses messenger molecules such as cytokines, which help activate T cells all over the body to prepare for defense against cancer, and chemokines, that direct T cells to the location of the tumor. However, the relationship between cancer cells and the immune system can get complicated, as tumors will do anything in their power to hide from the immune system and grow undetected. Think of cancer cells as enemy soldiers hiding in plain sight, dressed in civilian clothing. They evolve ways to remove or disguise their ID badges that avoids detection by T cells. So, while immune cells continue to patrol unaware, cancer cells grow unchecked.
Once they’ve gone undetected, cancer cells don’t just hide – they start rewriting the rules of the battlefield. They transform their surroundings into a space they fortify to block immune cells from entering, called a tumor microenvironment (TME). The TME is a space they control and manipulate to their advantage. Within this space, cancer cells manipulate the very tools meant to fight them. They deactivate T cells by displaying “stop” signals, putting them into a state of exhaustion where they can no longer function. At the same time, cancer reprograms cytokines and chemokines to recruit a special class of immune cells called regulatory T cells, or Tregs. These cells normally keep the immune system from overreacting and attacking the body’s own tissues. But in this context, they’re exploited to suppress the immune response against the tumor, protecting it from attack. By corrupting these immune signals, cancer creates a hostile environment for functional immune cells and secures its hold.
Cancers cells also become more aggressive at hiding from the immune system and spreading through the body. Imagine the original tumor as part of a tightly guarded fortress – cells that are stuck in place, well-organized, and connected like bricks in a wall. To break free of these constraints, cancer cells must undergo a process called epithelial-to-mesenchymal transition, or EMT. Through EMT, they lose their rigid structure, detach from their neighbors, and become flexible and mobile. Slipping past their fortress, these transformed cancer cells invade nearby tissues, enter the bloodstream, and colonize distant organs. By escaping their structured defense, cancers evade the immune system more aggressively and also make the disease much harder to treat in one location.
Because cancer uses so many survival and growth strategies, it isn’t a single enemy with a single weakness – it’s a complex, ever-evolving adversary. Understanding how tumors grow and evade the immune system is critical to designing treatments that can target different aspects of cancer growth. For instance, therapies are being developed to re-activate immune cells against cancer cells, and infiltrate and destroy the TME. Other therapeutic approaches also include blocking the “stop” signals cancer uses to avoid being killed, thus allowing immune cells to resume their attack. Targeting EMT can help prevent the cancer from gaining invasive traits and spreading. And by disrupting the cytokine signals that help build a tumor-friendly environment, we can restore normal immune function and give the body a fighting chance.
So, when scientists say they’re “working on a cure for cancer,” they’re really targeting one small piece of a much larger, shape-shifting puzzle. As we continue to uncover the rules of this molecular battleground, each discovery offers new ways to tip the balance in favor of the immune system. While there may never be a single cure, the growing ability to counter cancer’s diverse strategies brings us closer to making it a manageable, and hopefully conquerable disease.
References:
- Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther. 2021 May;221:107753. doi: 10.1016/j.pharmthera.2020.107753. Epub 2020 Nov 28. PMID: 33259885; PMCID: PMC8084948.
- Kartikasari AER, Huertas CS, Mitchell A, Plebanski M. Tumor-Induced Inflammatory Cytokines and the Emerging Diagnostic Devices for Cancer Detection and Prognosis. Front Oncol. 2021 Jul 7;11:692142. doi: 10.3389/fonc.2021.692142. PMID: 34307156; PMCID: PMC8294036.
- de Visser KE, Joyce JA. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell. 2023 Mar 13;41(3):374-403. doi: 10.1016/j.ccell.2023.02.016. PMID: 36917948.
- El-Kenawi A, Hänggi K, Ruffell B. The Immune Microenvironment and Cancer Metastasis. Cold Spring Harb Perspect Med. 2020 Apr 1;10(4):a037424. doi: 10.1101/cshperspect.a037424. PMID: 31501262; PMCID: PMC7117953
- Singh D, Siddique HR. Epithelial-to-mesenchymal transition in cancer progression: unraveling the immunosuppressive module driving therapy resistance. Cancer Metastasis Rev. 2024 Mar;43(1):155-173. doi: 10.1007/s10555-023-10141-y. Epub 2023 Sep 30. PMID: 37775641.
Author:
Anuli Khairatkar, holds a Bachelor’s degree in Biological Sciences and a Master’s degree in Pharmacogenomics, and spent four years in the San Diego biotech industry working on cutting-edge translational cancer immunotherapy. Her scientific background lies at the intersection of cancer therapeutics, immunology, and personalized medicine, which she is currently applying towards her PhD in Molecular Genetics and Immunology. Her passion for scientific communication stems from a deep interest in how research connects to real-world impact. She believes science should not live behind jargon – it should be accessible, clear, and engaging for everyone. Ultimately, she aims to help bridge the gap between science and society through scientific writing.
This article was written as part of Club SciWri’s first Science Writing Workshop, an initiative aimed at nurturing new voices in science communication and helping participants explore how to make complex ideas accessible to wider audiences.
Workshop conducted by Saurja Dasgupta, Sumbul Jawed Khan, Ananya Sen , Rohini Subrahmanyam, and Roopsha Sengupta
