Like a community, the tumor microenvironment (TME) has its own set of structures consisting of cells on the inside. Such a structure houses a variety of cells, including cancer cells, supporting cells, and, most importantly, immune cells that combat disease. A significant challenge in cancer treatment is that immune cells cannot effectively penetrate tumors, which hinders their ability to perform vital functions.
Cancer cells can create obstacles that prevent immune cells from getting to them. For example, they can lower the oxygen levels around immune cells or release substances that hide them from the immune system. These obstacles stop immune cells from working well, allowing cancer to grow and spread.
According to the blog “Tumor Microenvironment: The Hidden Barriers to Immune Cell Infiltration,” medicine development has challenges. Aiding these scientists in developing better cancer treatments and increasing patients’ survival rates by helping immune cells enter the tumor.
The Importance of Immune Cell Infiltration
In the same way that little soldiers defend us against threatening health issues such as cancer, immune cells serve the same purpose within our bodies. The infiltration of tumors by immune cells is a good indication for patients; however, these specific types of cells are highly regulated. Effector T cells are a crucial type of immune cell present in tumors, and they significantly contribute to improved outcomes and extended survival rates for patients with melanoma and ovarian cancer. Effector T cells are essential since they can specifically target and kill cancerous cells.
Conversely, certain tumors have evolved mechanisms to withhold themselves from effector immune cells. This has dire consequences, as immunoediting strategies dampen the efficacy of the immune system’s attempt to target the tumor. Balancing how these immune cells can permeate tumors is critical for the effectiveness of the treatments. As a result, scientists are trying to devise methods of encouraging more immune cells to invade the tumors so patients have a higher probability of recovery.
Mechanisms of Immune Evasion
- Vascular Barriers: Tumors, also known as cancer, develop vessels that are complicatedly out of proportion compared to the usual blood vessels found in a normal individual. These abnormal vessels are poorly constructed, which poses a problem for the immune cells to move in haste from the blood into the tumor. Specific cells in the blood vessels of the cancer construct immune inhibitory substances like PD-L1 and IDO, which provide the tumor an edge over the immune attack. These blockers are highly effective in turning off the immune system, making it arduous to reach the tumor site. In addition, tumors do not produce some of the signals known as chemokines that aid in the relocation of immune cells. These signals are crucial for the immune system’s effective recognition and destruction of the tumor, which makes targeting the cancer even more difficult. Even though the body has mechanisms to deactivate and cure cancer, tumors can erect obstacles to bypass such defensive measures.
- Extracellular Matrix (ECM) Components: Our body has a medium-thick web-like structure called the Extracellular Matrix that encapsulates tumor tissues. This web acts as a barrier to the mobility of immune cells, which are essential in obliterating sickness, and makes their way of seeking cancer cells difficult. A high collagen concentration, a protein constituent of the ECM, can block immune T cells from accessing the tumor region. Cancer-associated fibroblasts, or CAFs, are abnormal cells that cause modifications in the ECM and further immunosuppression. CAFs are known to interact with immune cells, and this interaction modifies the environment to promote immunosuppression and tumor development. This indicates that some parts of the tumor still function when our bodies are active against cancer, evading these immune attackers.
- Immunosuppressive Cell Populations: Our body possesses cells that fight against different ailments, but there are times when specific cells within the tumor’s microenvironment (TME) can limit these cells’ efficiency. One class of cells that interferes with the functioning of immune cells is called regulatory T cells or Tregs. Tregs can inhibit the functional activity of immune cells by contracting or suppressing activating signals sent to immune cells. This results in fewer immune cells that can target the tumor. Another group of cells, myeloid-derived suppressor cells (MDSC), also inhibits the effector functions of immune cells. MDSC can produce several factors that suppress T cell activity and development. Because of these cells, tumors can grow and thrive, which increases the difficulty of combating cancerous cells within the body’s immune system.
Strategies to Overcome Barriers
Scientists are putting their best efforts into our bodies’ immune systems to figure out methods for combating cancerous cells more effectively. Their focus is specifically on the tumor microenvironment (TME), similar to a neighborhood where cancerous cells reside and block immune cells from performing their functions. To resolve this situation, scientists are trying these solutions:
- Researchers To Improve Blood Vessels: Scientists have discovered that one solution is to fix the damaged, messy, and dysfunctional blood vessels around cancerous tumors. If more substantial blood vessels are developed, more immune cells can reach the cancerous cells and attack them. Researchers are actively pursuing medications that will effectively repair these blood vessels.
- Changing the Surrounding Tissue: Another hypothesis is that the stuff surrounding the tumor, known as extracellular matrix (ECM), can be changed. The ECM is very thick and sticky; immune cells are easily restricted. If scientists reduce the density of ECM or break it, then T cells, a type of immune cell that fights cancer, may be able to move more freely around the body.
- Targeting Bad Cells: Certain cells in the TME can interfere with the activity of immune cells. Such cells include only the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Scientists are working on strategies to eliminate or inhibit these bad cells so that good immune cells can infiltrate the tumor and deal with it without resistance.
- Boosting Chemical Signals: Scientists are also seeking ways to boost chemical signals or chemokines, which draw immune cells towards tumors. The expectation is to enhance the signals or stimulate the body to produce more signals to recruit immune fighters to the cancer battleground.
Using combinations of the above strategies, researchers hope to destroy the TME walls and improve the efficacy of our immune system. This will make treatments for cancer patients more effective.
Conclusion
The tumor microenvironment makes it difficult for immune cells to enter, which affects how cancer grows and responds to treatment. To create new ways to boost the body’s anti-cancer response, we need to understand how these barriers form. Scientists are looking at several methods to overcome these challenges and improve immunotherapy. These techniques include eliminating immune suppressive cells, modifying the architecture of the surrounding tissues, modifying blood vessels, and increasing the signals that recruit immune cells.
The more we fight to understand the tumor microenvironment, the better strategies we can develop for harnessing the immune system against cancer. In this regard, performing more research is promising to make cancer therapy more efficacious and tailored to patients irrespective of geography.