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Unraveling the Mysteries: How CD44 and CD62L Shape the Fates of Tumor Cells and T Cells
CD44 and CD62L are two molecular markers on the T cell surface that play a crucial role in the regulation of T cell activation, migration, and function. Today, Xiao Ai will show you the marking effects of these two indicators on tumor cells and T cells.
CD44 is a transmembrane glycoprotein belonging to the integrin family. It is widely expressed in various cell types, including leukocytes, endothelial cells, fibroblasts, and certain tumor cells.
Cell adhesion and migration: CD44 participates in cell adhesion, migration, and signal transduction by binding to hyaluronic acid (HA). In immune cells, CD44 helps T cells and B cells to position and migrate in lymphoid tissues.
Tumor biology: CD44 is one of the markers of tumor stem cells and is involved in tumor cell proliferation, migration, and invasion. Tumor cells with high CD44 expression usually have stronger metastatic ability and drug resistance.
Immune regulation: CD44 also plays a regulatory role in immune responses, influencing T cell activation and function.
I. The relationship between CD44 and T cells and B cells
Migration and positioning: CD44 helps T cells and B cells migrate and position in lymphoid tissues by binding to hyaluronic acid (HA). In lymph nodes, CD44-mediated cell-matrix interactions contribute to immune cell homing and retention.
Immune activation: CD44 also plays an auxiliary role in the activation of T cells and B cells. By binding to HA, CD44 can enhance the interaction between immune cells and antigen-presenting cells (APCs), promoting the initiation of immune responses.
Adhesion and migration: CD44 regulates T cell migration and positioning in lymphoid tissues, inflammatory sites, and target tissues by interacting with adhesion and matrix molecules.
Activation signal transduction: CD44 interacts with other surface receptors (such as TCR and co-stimulatory molecules) to enhance T cell activation signal transduction, promoting cell proliferation and functional exertion.
Storage memory: CD44 plays an important role in the formation and maintenance of long-term immune memory, helping T cells to rapidly initiate responses upon encountering the same antigen again.
Tumor cell marking: CD44 is one of the most common markers of tumor stem cells and is involved in tumor cell metastasis, adhesion, and migration.
II. The relationship between CD44 and natural killer cells (NK cells)
Cytotoxicity: CD44 also plays a role in the cytotoxicity of NK cells. NK cells with high CD44 expression have stronger cytotoxicity and can more effectively kill target cells.
Tumor microenvironment: In the tumor microenvironment, tumor cells with high CD44 expression can interact with immune cells, affecting their function. For example, CD44 can form an immunosuppressive microenvironment by binding to HA, inhibiting T cell activity.
Immune evasion: Tumor cells with high CD44 expression have stronger immune evasion ability and can avoid recognition and killing by immune cells through various mechanisms.
CD62L (L-selectin) is an adhesion molecule belonging to the selectin family. It is mainly expressed on the surface of leukocytes, including T cells, B cells, and natural killer cells.
Cell homing: CD62L plays a key role in leukocyte homing, helping leukocytes move from the blood to lymphoid tissues. In inflammatory responses, CD62L mediates the initial adhesion of leukocytes to endothelial cells.
Immune cell positioning: CD62L helps T cells and B cells position in lymph nodes and participate in the initiation and regulation of immune responses.
Immune memory: T cells with high CD62L expression usually have the characteristics of central memory T cells (Tcm), which can rapidly respond upon re-encountering antigens.
III. The relationship between CD62L and T cells and B cells
Homing: CD62L plays a key role in leukocyte homing, helping T cells and B cells move from the blood to lymphoid tissues. In inflammatory responses, CD62L mediates the initial adhesion of leukocytes to endothelial cells, promoting leukocyte rolling and migration.
Immune response: By promoting the positioning of T cells and B cells in lymph nodes, CD62L helps initiate and regulate immune responses. T cells with high CD62L expression usually have the characteristics of central memory T cells (Tcm), which can rapidly respond upon re-encountering antigens.
Non-activated state recognition: In the non-activated state, CD62L expression enables T cells to recognize and enter secondary lymphoid organs such as lymph nodes, participating in the initiation of immune responses.
Central memory cell marker: CD62L is considered a marker of central memory T cells, which have high CD62L expression and the ability to quickly locate to positions such as lymph nodes for rapid secondary responses.
IV. The relationship between CD62L and natural killer cells (NK cells)
Migration and positioning: CD62L also participates in the migration and positioning of NK cells, helping them gather at inflammatory sites and enhancing their cytotoxic function.
Immune cell distribution: CD62L regulates the distribution of immune cells in different tissues, affecting the intensity and duration of immune responses. For example, T cells with high CD62L expression stay longer in lymph nodes and can more effectively participate in immune responses.
V. Distinguishing T cell subsets through CD44 and CD62L
Naive T cells: CD44low/- CD62L+
Central memory T cells (Tcm): CD44high CD62L+
Effector memory T cells (Tem) or effector T cells (Teff): CD44high CD62L-
VI. Additional markers for distinguishing Tem and Teff
CD127 (IL-7Rα): Usually expressed in Tem, while expression is reduced in Teff.
KLRG1: Highly expressed in Teff, with lower expression in Tem.
CD69: Highly expressed in early-activated Teff.
Bcl-2: Highly expressed in Tem, with lower expression in Teff.
Cytokine production: Detect IFN-γ, TNF-α, IL-2, etc.
Proliferative capacity: Tem usually has stronger proliferative potential.
Through these markers and functional tests, different types of T cells can be more accurately distinguished, thereby better understanding immune responses and disease mechanisms.
VII. Potential applications of CD44 and CD62L in cancer therapy
Drug delivery: CD44 is the receptor for hyaluronic acid (HA), which can serve as a drug carrier to deliver cytotoxic drugs or prodrug convertases to the vicinity of tumor cells, forming a cytotoxic barrier and thereby enhancing anti-tumor effects. For example, HA-modified liposomes have shown excellent anti-tumor activity in vitro and in mouse tumor models.
Antibody conjugates: Anti-CD44 antibodies can be used to deliver radioactive isotopes or cytotoxic drugs to treat tumors expressing CD44. In early clinical trials, patients with breast or head and neck tumors treated with anti-CD44 conjugates showed stable disease.
Enhancing immune response: Tumor cells with high CD44 expression can be treated with immune checkpoint inhibitors (such as PD-1/PD-L1 inhibitors) in combination therapy to enhance anti-tumor effects. For example, the MUSIC treatment strategy combined with PD-1 inhibitors not only showed stronger primary tumor suppression but also significantly slowed tumor metastasis, increasing the median survival time of mice in the combination therapy group by 76%.
Predicting immune therapy response: CD44 is a promising biomarker for predicting immune therapy response and mediating PD-L1 expression. In bladder cancer, high CD44 expression is associated with poor patient prognosis and positively correlates with PD-L1 expression.
Enhancing T cell infiltration: CD62L-positive T cells can enter secondary lymphoid organs such as lymph nodes to participate in immune responses. By regulating CD62L expression, T cell infiltration in the tumor microenvironment can be enhanced, thereby improving the efficacy of immunotherapy.
Combination Therapy: T cells with high CD62L expression demonstrate superior antitumor efficacy in combination therapy. For instance, the MUSIC therapeutic strategy in conjunction with a PD-1 inhibitor not only enhances the suppression of primary tumors but also significantly retards tumor metastasis.
Regulating Imm Cellune Distribution: CD62L regulates the distribution of T cells within the tumor microenvironment. Increasing the number of CD62L-positive T cells can strengthen immune surveillance and the antitumor response.
Summary
CD44 is primarily involved in cell adhesion, migration, and tumor biology, serving as a tumor stem cell marker with significant clinical utility. Due to its high expression in tumor stem cells, CD44 has emerged as a potential therapeutic target. Targeting CD44 can inhibit tumor cell proliferation and metastasis, thereby potentiating antitumor effects. In cancer therapy, its applications are mainly through targeted drug delivery enhanced, immune responses, and modulation of the tumor microenvironment. Its high expression correlates with poor prognoses in various cancers, positioning it as a promising therapeutic target.
CD62L is mainly involved in leukocyte homing and the positioning of immune cells, serving as a central memory T cell marker of great significance in immunotherapy. In cancer treatment, it enhances the efficacy of immunotherapy primarily by increasing T cell and infiltration regulating immune cell distribution. In CAR-T cell therapy, selecting T cells with high CD62L expression can improve the efficacy and persistence of CAR-T cells. Combination therapies can significantly enhance antitumor effects and reduce tumor metastasis.
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May 06, 2025
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