They are cells that form part of the immune system that protects the organism from germs (bacteria or viruses) producing proteins called antibodies. Antibodies adhere to germs, and mark them to be destroyed by other immune system components.
Non-Hodgkin’s lymphoma (NHL)
Non-Hodgkin’s lymphoma (also known simply as lymphoma) is a cancer that originates in the white blood cells called lymphocytes that form part of the immune system. The most frequent is composed of B-lymphocytes (B-NHL).
Diffuse large-cell lymphoma (DLBCL)
It is an aggressive B-NHL and therefore tends to grow rapidly. It constitutes the most frequent NHL and is a very heterogeneous disease. It presents in middle-aged and advanced aged adults. It is characterized by large cancerous cells that may be in the lymph nodes and extra lymphatic tissue. Standard treatment is immuno-chemotherapy, usually with a regimen of four drugs known as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) plus the monoclonal antibody rituximab (Rituxan). This regimen, known as R-CHOP, is administered most frequently in 3 week cycles.
Follicular lymphoma (FL)
B-NHL is usually indolent (slow-growing) and is the second most frequent after diffuse large-cell lymphoma. Tumor cells grow in groups to form nodules, hence their denomination of follicular. The disease is characterized by a good initial response (in general the therapy is R-CHOP as in DLBCL) but is often followed by relapses, which in a third of the cases transforms to an aggressive lymphoma.
Mantle cell lymphoma (MCL)
B-NHL of low incidence and rapid growth in most cases. It presents in middle-aged and elderly adults. It is characterized by small to medium-sized cancerous cells that may be in the lymph nodes, spleen, bone marrow, blood, and digestive tract. Current treatments include chemo immunotherapy regimens as first line, and targeted therapies for second line.
Chronic lymphatic leukemia (B-CLL)
It is a type of chronic lymphoproliferative syndrome of B lymphocytes with leukemic expression, i.e. in blood, but it is also found in the bone marrow and the organs of the lymphatic system. CLL is the most common leukemia in Western countries (20-40% of total leukemia) and affects people over 60 years of age. CLL is an heterogeneous and In many cases people who suffer from this disease have no symptoms for years, while others present a more aggressive disease.
Immunotherapy is a biological therapy that stimulates the immune system of the organism in order to fight cancer, among other diseases. The active molecules involved in immunotherapy are called immunomodulators.
A 3-D cell culture is an artificially created environment in which cells can grow or interact with their environment in the three dimensions. This is an improvement on the classic method of cells that grow in 2-D, because the 3-D culture recapitulates the in vivo models better. These three-dimensional cultures are generally cultivated in bioreactors, small capsules in which cells can grow in spheroids or in 3-D colonies.
They are three-dimensional structures of about one millimeter in size, formed by cells that are distributed as they would be in an organ or tissue.
NGS -Next Generation Sequencing
The concept of NGS serves to encompass all the technologies intended to carry out the massive mass sequencing of any nucleic acid.
A nucleoside that is made up of adenine and D-ribose. Adenosine is a signaling molecule used by the body to limit inflammation and immune response. Many different types of tumors produce and actively maintain high levels of adenosine within the tumor microenvironment. Adenosine hinders the immune system’s ability to attack the tumor, mainly in two ways: (1) by blocking the activation and efficacy of immune cells that are capable of destroying tumor cells, and (2) by increasing the number of regulatory T cells (Tregs) that act to prevent immune cells from responding to the tumor. As tumor cells evolve and form tumor masses, they use these processes to evade the immune attack and promote their own survival.
Adenosine that produces tumors interacts with adenosine receptors on the surface of invasive immune cells. A type of adenosine receptor known as A2A is expressed in several cells of the immune system, which include T cells, NK cells, macrophages and dendritic cells. The adenosine junction to the A2A receptor has the effect of attenuating the immune cells ‘ ability to attack tumors. A significant number of scientific data indicate that directing the adenosine axis through the A2A receptor can promote anti-tumor immune responses, leading to tumor regression.
Adenosine carries out its biological effects through four subtypes of receptors, called:, A1, A2A, A2B and A3. The A1 and A2A have a high affinity for adenosine, while A2B and A3 show a relatively minor affinity. These receptors belong to the superfamily of G protein-coupled receptors (GPCR).
The A1 and A3 receptors are coupled to proteins G inhibitory Gi/o, while A2AAR and A2BAR are coupled to proteins stimulating Gs/olf. Therefore, the activation of the A2A and A2BAR increases the production of cyclic AMP, resulting in the activation of protein kinase A (PKA) and the phosphorylation of the protein binding to the response element cyclic AMP (CREB). Contrarily, the activation of A1 and A3 inhibits the production of cyclic AMP and decreases the activity of PKA and the phosphorylation of CREB.
Immune Check Point inhibitor
The maintenance of the immune homeostasis (equilibrium) is critical for the survival of the organism. Uncontrolled responses immune to mutated or over-expressed pathogens or auto-antigens can cause inflammation or auto-immune diseases. To avoid this, the immune response is regulated by a balance of activating and inhibitor signals, called immune check points (E.G. PD-1, CTL-4). Currently, tumors are known to manipulate these systems to become invisible to the immune system. New cancer therapies allow blocking these control points with inhibitors to make tumors visible so that the immune system can detect and eradicate them.
Selective Plane Illumination Microscopy is a light sheet illumination microscope that has been optimized to visualize specimens (organs, tissues), by fast sectioning in 3-D and in depth. This way, it is possible to capture the whole image in a short time, reducing sample bleaching, in samples upto 1mm (in the case of macro-SPIM)