Two groups of immune system mechanisms are important in cancer immunology: 1. Humoral immunology 2. Cellular immunology
B cells with inducible immune effects interact directly with T cells through TCR receptor mediation through antibody production. Antibodies that bind to surface proteins on tumor cells kill cancer cells by bridging the target through complement activation.
In this process, known as ADCC (Antibody-Dependent Cell Mediated Cytotoxicity), the Fab region of the antibody on the immune elements binds to the tumor antigen proteins and the cell by Fc, and also binds to the receptors of T cytotoxic cells (TCR), and in this case, the cancer cell T-cytotoxic cells. being killed by At the same time, the cancer cell can normally undergo apoptosis (programmed cell death) in the case of Fas-Fas L junction. The antibody is highly potent for cytotoxicity and the humoral response is important in tumor immunity, but the convincing evidence that antibody responses play a critical role in antitumor immunity in-vivo and in-vitro is weak.
Cells that are very important in tumor immunity:
1. Dendritic Cells
2. T Lymphocytes
3. NK Cells
4. Regulatory T Cells
Dendritic Cells:
Dendritic cells are professional APC cells that are active during the innate immune response and are equipped to receive and present antigen to effector cells (antigen-specific CD4 and CD8 T cells) of the specialized adaptive immune system. Dendritic cells are so named because of their pseudopods (dendrites) that extend to present antigen. It can occur by tumor cells presenting antigen directly to T cells to induce an antitumor response, but a more common and robust pathway for tumor-specific T cell activation in vivo is thought to be cross-presentation. During this process, antigens released from tumor cells that have undergone necrotic or apoptotic death are taken up and degraded by dendritic cells and then presented to T cells under appropriate conditions.
T Lymphocytes:
T cells consist of two important groups:
Helper T (CD4+)
Cytotoxic T (CD8+)
Helper T cells recognize antigen at MHCII binding and are divided into TH1 and TH2 subgroups on the basis of their different properties (cytokine and receptor profiles). TH1 CD4+ cells produce IL-2 and interferon-γ, express IL-12 and IL-18 receptors, and regulate T cells. TH2 cells produce IL-13, IL-14 and IL-15, and B cells regulate immunity. In this case, a TH1-type response may be a useful response in antitumor immunity to activate T cells.
Cytotoxic CD8+ T cells recognize antigen at the MHCI junction and poke holes in the memberan of the target cell, facilitating the entry of enzymatic packages (granzyme A and B) and releasing perforin and toxic granules to the membrane, directly mediating cell killing.
T cell peptides only recognize MHC complex binding, so a mutation affecting any component of antigen presenting cells can abolish specific T cells recognition and kill tumor cells.
Although cytotoxic T cells (CTLs) have a major role as seen in most studies, the vital role of helper CD4 T cells in inducing and maintaining an effective antitumor immune response to destroy tumor cells should not be overlooked. Tumor antigen-specific responses have been described for CD4 T-cells, but the presence and coordinated functioning of CD4 T-cells is required for CTL cells to respond to tumors.
NK Cells:
NK (Natural Killer) cells are activated during the response of natural killer cells and the inflammatory environment. The activity of NK cells is not antigen-specific and they do not express TCRs, but their interaction with tumor-derived ligands such as MICA and MICB overexpressed in tumor cells via Killer Activating Receptors (KARs) expressed on the surface of cells leads to NK activation in stressed and infected cells such as tumor cells. and kills the tumor. It is known that the increase in NK type cells in-vivo and at the same time high-dose IL-2 therapy are one of the important mechanisms that show clinical effects in the treatment of metastatic melanoma and kidney cancer.
Regulatory T Cells:
Regulatory T cells (Tregs) are two subsets and naturally occurring T regulatory cells represent 5-10% of the body. These cells with regulatory effects controlling autoimmune and antitumor responses were identified in 1975, but finding convincing evidence for their existence was difficult in the same years. Later, the CD4+ and CD25+ population of T cells with immunosuppressive function were identified, leading to an understanding of the role of regulatory T cells. Today, these cells are used in autoimmune diseases and antitumor activity.
Öğretim Görevlisi Masoumeh Hassani
