Tumor microenvironment (TME) refers to a complex ecosystem composed of tumor cells and their surrounding cellular and non cellular components. It not only includes blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules, and extracellular matrix (ECM), but also involves dynamic interactions between tumor cells and these components. With the deepening of research, the tumor microenvironment has become the forefront of cancer biology research and an important target for precision medicine and immunotherapy strategies. This article will delve into the composition, function, dynamic changes, and role of the tumor microenvironment in the occurrence, development, and metastasis of cancer.

1、Composition of tumor microenvironment

The tumor microenvironment is composed of multiple cell types, not limited to tumor cells themselves, but also including immune cells, fibroblasts, endothelial cells, smooth muscle cells, and so on. These cells play different roles in the occurrence, development, and metastasis of tumors.

1. Immune cells: The tumor microenvironment contains various immune cells, such as T cells, B cells, macrophages, dendritic cells, natural killer cells (NK cells), etc. These cells play important roles in tumor immune surveillance, immune escape, and immune suppression. For example, adaptive immune cells (such as CD8+T cells) can recognize and kill tumor cells, while immunosuppressive cells (such as regulatory T cells, Tregs) can suppress this immune response.

2. Stromal cells: Fibroblasts, especially cancer associated fibroblasts (CAFs), are an important component of the tumor microenvironment. They promote the growth and metastasis of tumor cells by secreting cytokines, chemokines, and ECM components. In addition, endothelial cells and vascular cells also provide oxygen and nutrients to tumors by forming a new vascular network.

3. Other cells: The tumor microenvironment also includes smooth muscle cells, adipocytes, glial cells, etc. They participate in the construction and regulation of the tumor microenvironment by secreting various bioactive molecules.

4. Non cellular components: In addition to cellular components, the tumor microenvironment also includes various non cellular components such as ECM, growth factors, cytokines, chemokines, etc. These components regulate the biological behaviors of tumor cells, such as growth, proliferation, migration, and invasion, through complex signaling networks.

2、Dynamic changes in tumor microenvironment

1. Initial stage of cancer: In the initial stage of cancer, malignant cells begin to grow uncontrollably and are recognized by both innate and adaptive immune systems. At this point, various B cells, T cells, myeloid immune cells, etc. begin to accumulate at the site of tumor cells, forming a preliminary immune monitoring network. However, as cancer cells continue to proliferate and differentiate, they gradually evade the monitoring and clearance of the immune system, forming an immune escape tumor microenvironment.

2. Cancer progression stage: As the cancer progresses, the tumor microenvironment undergoes significant changes. On the one hand, the number and function of immune cells gradually decrease, especially the reduction and dysfunction of cytotoxic immune cells such as CD8+T cells and NK cells; On the other hand, the number of immune suppressive cells (such as Tregs and MDSCs) gradually increases and secretes various immune suppressive factors, inhibiting the anti-tumor activity of immune cells. In addition, stromal cells such as tumor associated fibroblasts (CAFs) and endothelial cells also promote the growth and metastasis of tumor cells by secreting cytokines and ECM components.

3. Cancer metastasis stage: During the cancer metastasis stage, tumor cells undergo a series of complex biological processes, such as epithelial mesenchymal transition (EMT), crossing the endothelial layer, infiltrating blood vessels and lymphatic vessels, etc., detaching from the primary lesion and spreading to distant organs. During this process, the tumor microenvironment forms a pre metastatic niche in the distal region through mechanisms such as paracrine secretion, providing conditions for cancer cell metastasis and colonization. At the same time, metastatic tumor cells also interact with the new microenvironment in distant organs, forming a new tumor microenvironment and continuing to grow and spread

3、Tumor microenvironment and immunotherapy

1. Immune checkpoint inhibitors: Immune checkpoint inhibition is currently one of the important means of tumor immunotherapy. It restores the anti-tumor activity of immune cells by blocking the binding between inhibitory receptors (such as PD-1) on the surface of immune cells and their ligands (such as PD-L1). However, the efficacy of immune checkpoint inhibitors is limited in "cold" tumors (i.e. tumors with high immune cell suppression and low immune infiltration). Therefore, understanding and regulating the immunosuppressive mechanisms in the tumor microenvironment is crucial for improving the efficacy of immune checkpoint inhibitors.

2. Tumor infiltrating lymphocyte (TILs) therapy: Tumor infiltrating lymphocyte therapy is a novel immunotherapy method that isolates TILs from the patient's tumor tissue, amplifies and activates them in vitro, and transfers them back into the patient's body. TILs can specifically recognize and kill tumor cells, and have sustained anti-tumor activity in vivo. However, TIL therapy also faces some challenges, such as isolation, amplification, and quality control of TIL. In addition, how to optimize the immune microenvironment of TIL and improve its efficacy and safety is also one of the current research hotspots.

3. Regulation of tumor associated macrophages (TAMs): Tumor associated macrophages are an important immune cell population in the tumor microenvironment, with high heterogeneity and different functions depending on their polarization state (M1 or M2). M1 type TAMs have anti-tumor activity, while M2 type TAMs promote tumor growth and metastasis. Therefore, by regulating the polarization state of TAMs, the immune balance of the tumor microenvironment can be affected, thereby affecting the therapeutic effect of tumors. Currently, some research is dedicated to developing targeted drugs for TAM to alter its polarization state and enhance anti-tumor immune response.

4. Cancer vaccines: Cancer vaccines are another promising immunotherapy that recognizes and eliminates tumor cells by activating the patient's own immune system. Cancer vaccines can contain tumor specific antigens, immune adjuvants, or other immune stimulatory substances to stimulate the body to produce specific immune responses against tumor cells. However, due to the heterogeneity of tumor cells and the existence of immune escape mechanisms, the development and application of cancer vaccines also face many challenges. In the future, by gaining a deeper understanding of the immune regulatory mechanisms in the tumor microenvironment, more effective cancer vaccines can be designed to improve patient survival rates and quality of life.

The tumor microenvironment, as a complex ecosystem, plays a crucial role in the occurrence, development, and metastasis of cancer. By delving into the composition, function, and dynamic changes of the tumor microenvironment, we can better understand the biological behavior of cancer and develop more effective diagnostic and treatment strategies. In the future, with the launch of the Beacon device by Redbert (Beijing) Biotechnology Co., Ltd., it can save you a lot of screening time and greatly reduce production costs. The Beacon Optofluidic System can directly operate and cultivate individual target cells from the beginning of the experiment, with highly reliable and efficient results. This system combines unique optoelectronic positioning technology with innovative nanofluidic design, enabling fully automated experimental operations such as import, culture, detection, and export of single cells or monoclonal antibodies, providing an integrated and efficient research platform for all single-cell based development and applications. We have reason to believe that the tumor microenvironment will become one of the important targets for cancer treatment, bringing hope and good news to more cancer patients. At the same time, we also need to recognize that the complexity and heterogeneity of the tumor microenvironment remain one of the main challenges facing current research, requiring us to continue exploring and innovating.

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