Tumorimmunology 2019

A primary brain tumor is one that originates in the brain, and not all primary brain tumors are cancerous; benign tumors are not aggressive and normally do not spread to surrounding tissues, although they can be serious and even life threatening. Primary brain tumors emerge from the various cells that make up the brain and central nervous system and are named for the kind of cell in which they first form. The most common types of adult brain tumors are gliomas and astrocytic tumors. These tumors form from astrocytes and other types of glial cells, which are cells that help keep nerves healthy. The second most common type of adult brain tumors are meningeal tumors. These form in the meninges, the thin layer of tissue that covers the brain and spinal cord.

The molecular classification of Tumor is actually arrangement analysis disguised as classification. In a typical gene expression array study, the researcher will look at a cluster of tumors of a specific type. Cluster analysis of the gene expression array values will help discrete the tumors into groups with common expression patterns. Some of these groupings will prove to have a detailed biologic feature (e.g. increased tendency to metastasize, higher response to a chemotherapeutic agent, lengthened existence). Cancers are not just masses of malignant cells but complex ‘rogue’ organs, to which many other cells are recruited and can be degraded by the transformed cells. Interactions between malignant and non-transformed cells create the Tumor microenvironment (TME).

Immunotherapy is an innovative treatment approach that empowers the human immune system to overcome cancer and other debilitating diseases. The T-cell therapies are the most radical of several new approaches that recruit the immune system to attack cancers. The treatments work by removing molecular brakes that normally keep the body’s T cells from seeing cancer as an enemy, and they have helped demonstrate that the immune system is capable of destroying cancer. Immunotherapy may help boost the body’s immune response. This approach uses drugs/agents to trigger or stimulate the immune system to react to the invader – in this case, the cancer cells. This is similar to how a cold virus would stimulate your immune system.

Immunotherapy is treatment that uses certain parts of a person’s immune system to fight diseases such as cancer. This can be done in a couple of ways: Own immune system stimulation, Biological therapy or biotherapy. These advances in cancer immunotherapy are the result of long-term investments in basic research on the immune system—research that continues today. Additional research is currently under way to: understand why immunotherapy is effective in some patients but not in other’s who have the same cancer, expand the use of immunotherapy to more types of cancer, increase the effectiveness of immunotherapy by combining it with other types of cancer treatment, such as targeted therapy, chemotherapy, and radiation therapy.

Cancer is the name given to a collection of related diseases. Cancer can start almost anywhere in the human body, which is made up of trillions of cells. In all types of cancer, some of the body’s cells begin to divide without stopping and spread into surrounding tissues. When cancer develops, however, this orderly process breaks down. As cells become more and more abnormal, old or damaged cells survive when they should die, and new cells form when they are not needed. These extra cells can divide without stopping and may form growths called tumors. There are more than 100 types of cancer. Types of cancer are usually named for the organs or tissues where the cancers form. For example, lung cancer starts in cells of the lung, and brain cancer starts in cells of the brain. Cancers also may be described by the type of cell that formed them, such as an epithelial cell or a squamous cell.

The goal of the Cancer Research Program is to make significant improvements in the prevention, early detection, diagnosis and treatment of cancer. It will continue to translate basic research findings into clinical applications together with strategic partners, with the National Centre for Tumor Diseases (NCT) and the nationally active German Consortium for Translational Cancer Research (DKTK) playing key roles. Most of us know about vaccines given to healthy people to help prevent infections, such as measles and chicken pox. These vaccines use weakened or killed germs like viruses or bacteria to start an immune response in the body. Getting the immune system ready to defend against these germs helps keep people from getting infections. Most cancer vaccines work the same way, but they make the person’s immune system attack cancer cells. 

Antibody marks the cancer cell and makes it easier for the immune system to find. The monoclonal antibody drug rituximab (Rituxan) attaches to a specific protein (CD20) found only on B cells, one type of white blood cell. Certain types of lymphomas arise from these same B cells. Monoclonal antibodies can also function by attenuating hyperactive growth signals neo angiogenesis. A monoclonal antibody can be conjugated to a radioactive particle that will ensure directed delivery to the cancer cell and slow and long release of the radiation, hence maximizing chances of positive outcome and minimizing non-specific damaging exposure to radiation.

Targeted therapies act by blocking essential biochemical pathways or mutant proteins that are required for tumor cell growth and survival. These drugs can arrest tumor progression and induce striking regressions in molecularly defined subsets of patients. Indeed, the first small molecule targeted agent, the BCR-ABL kinase inhibitor imatinib, rapidly induced complete cytogenetic responses in 76% of chronic myelogenous leukemia patients. Further research into the underlying genetic pathways driving tumor proliferation uncovered additional oncoproteins that are critical for tumor maintenance, such as the epidermal growth factor receptor (EGFR), BRAF, KIT, HER (also known as neu and ERBB) and anaplastic lymphoma kinase (ALK). Similar to imatinib, small molecule inhibitors of these kinases have effectuated impressive tumor responses in selected patients, although regressions are commonly followed by the development of progressive disease due to the emergence of drug-resistant variants. Resistance usually involves secondary mutations within the targeted protein or compensatory changes within the targeted pathway that bypass the drug-mediated inhibition. Accordingly, targeted therapies may elicit dramatic tumor regressions, but persistence is generally short-lived, limiting the overall clinical benefit.

Immunology-based therapy is rapidly developing into an effective treatment option for a surprising range of cancers. We have learned over the last decade that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called "immune checkpoints." The development of a new therapeutic class of drugs that inhibit these inhibitory pathways has recently emerged as a potent strategy in oncology. Three sets of agents have emerged in clinical trials exploiting this strategy. These agents are antibody-based therapies targeting cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). These inhibitors of immune inhibition have demonstrated extensive activity as single agents and in combinations. Clinical responses have been seen in melanoma, renal cell carcinoma, small cell lung cancer, and several other tumor types.

To developing new methods to prevent, detect, and treat cancer. It is through clinical trials that researchers can determine whether new treatments are safe and effective and work better than current treatments. Cancer clinical trials have led to scientific advances that have increased doctors' understanding of how and why tumor’s develop and grow. This knowledge has helped doctors make progress in preventing cancer, diagnosing cancer, slowing or stopping the development of cancer, and finding cancers that have come back after treatment.

Radiology represents a branch of medicine that deals with radiant energy in the diagnosis and treatment of dise.  An imaging test is a way to let doctors see what’s going on inside your body. These tests send forms of energy (like x-rays, sound waves, radioactive particles, or magnetic fields) through your body. Your body tissues change the energy patterns to make an image or picture. These pictures show how your insides look and work so that health care providers can see changes that may be caused by diseases like cancer. 

Prognosis of any disease means the estimate of the likely course and outcome of the disease. Prognosis of cancers usually means the estimate of success with treatment and chances of recovery.  Doctors estimate prognosis by using statistics that researchers have collected over many years about people with the same type of cancer. Several types of statistics may be used to estimate prognosis. Some common numbers that are used to determine prognosis include cancer specific survival, relative survival, overall survival, disease-free survival etc. Cancer is nearly always diagnosed by an expert who has looked at cell or tissue samples under a microscope. In some cases, tests done on the cells’ proteins, DNA, and RNA can help tell doctors if there’s cancer. These test results are very important when choosing the best treatment options. Lumps that could be cancer might be found by imaging tests or felt as lumps during a physical exam, but they still must be sampled and looked at under a microscope to find out what they really are. Not all lumps are cancer. In fact, most tumors are not cancer.

Interactions between malignant and non-transformed cells create the Tumor microenvironment (TME). The non-malignant cells of the TME have a dynamic and often tumor-promoting function at all stages of carcinogenesis .Intercellular communication is driven by a complex and dynamic network of cytokines, chemokine’s, growth factors, and inflammatory and matrix remodeling enzymes against a background of major perturbations to the physical and chemical properties of the tissue. The evolution, structure and activities of the cells in the TME have many parallels with the processes of wound healing and inflammation, but cells such as macrophages are also found in cancers that have no known association with chronic inflammatory conditions. 

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is the most widely used stem-cell therapy; Stem-cell therapy has become controversial following developments such as the ability of scientists to isolate and culture embryonic stem cells, to create stem cells using somatic cell nuclear transfer and their use of techniques to create induced pluripotent stem cells. For over 30 years, bone marrow has been used to treat cancer patients with conditions such as leukaemia and lymphoma; this is the only form of stem-cell therapy that is widely practiced. Stem cells are being studied for a number of reasons. The molecules and exosomes released from stem cells are also being studied in an effort to make medications

Tumor markers are substances that are produced by cancer or by other cells of the body in response to cancer or certain benign (noncancerous) conditions. Most tumor markers are made by normal cells as well as by cancer cells; however, they are produced at much higher levels in cancerous conditions. These substances can be found in the blood, urine, stool, tumor tissue, or other tissues or bodily fluids of some patients with cancer. Most tumor markers are proteins. Thus far, more than 20 different tumor markers have been characterized and are in clinical use. Some are associated with only one type of cancer, whereas others are associated with two or more cancer types. There is no “universal” tumor marker that can detect any type of cancer. Among various approaches to specifically target drug-loaded carrier systems to required pathological sites in the body, two seem to be most advanced – passive (EPR effect-mediated) targeting, based on the longevity of the pharmaceutical carrier in the blood and its accumulation in pathological sites with compromised vasculature, and active targeting, based on the attachment of specific ligands to the surface of pharmaceutical carriers to recognize and bind pathological cells. 

Cancer cells behave as independent cells, growing without control to form tumors. Tumors grow in a series of steps. The first step is hyperplasia, meaning that there are too many cells resulting from uncontrolled cell division. These cells appear normal, but changes have occurred that result in some loss of control of growth. The second step is dysplasia, resulting from further growth, accompanied by abnormal changes to the cells. The third step requires additional changes, which result in cells that are even more abnormal and can now spread over a wider area of tissue. These cells begin to lose their original function; such cells are called anaplastic. At this stage, because the tumor is still contained within its original location (called in situ) and is not invasive, it is not considered malignant - it is potentially malignant. The last step occurs when the cells in the tumor metastasize, which means that they can invade surrounding tissue, including the bloodstream, and spread to other locations. This is the most serious type of tumor, but not all tumors progress to this point. Non-invasive tumors are said to be benign. The discovery of tumor stem cells in a range of cancers has created opportunities for researchers to identify these rare cells in both solid tumors and hematologic cancers, as well as to investigate the role of these cells at different stages of disease.The recognition that the cancer cell is in a symbiotic relationship with the tumor microenvironment has created opportunities to study the interactions of cancer cells within the tumor or the host microenvironment.

Cancer Pharmacology focuses on developing experimental approaches to the clinical treatment of cancer through research that bridges the fields of molecular carcinogenesis, biochemical pharmacology, radiation biology, and clinical pharmacology. Cancer chemotherapy and pharmacology involves the pharmacological and oncological aspects of drugs at both an experimental and clinical level. New anticancer drugs require screening in terms of not only their pharmacokinetic and pharmacodynamic profiles but also single and combined drug administration modalities as well as the different phases of clinical trials. Importantly preclinical toxicology as well as drug interactions and indications for chemotherapy in cancer treatment are also investigated. 

In cancer research and medicine, biomarkers are used in three primary ways:

• To help diagnose conditions, as in the case of identifying early stage cancers (Diagnostic)
• To forecast how aggressive a condition is, as in the case of determining a patient's ability to fare in the absence of treatment (Prognostic)
• To predict how well a patient will respond to treatment (Predictive)

Cancer genomics is the study of the totality of DNA sequence and gene expression differences between tumour cells and normal host cells. It aims to understand the genetic basis of tumour cell proliferation and the evolution of the cancer genome under mutation and selection by the body environment, the immune system and therapeutic interventions. Metabolomics research is being used to discover diagnostic cancer biomarkers in the clinic, to better understand its complex heterogeneous nature, to discover pathways involved in cancer that could be used for new targets and to monitor metabolic biomarkers during therapeutic intervention. These metabolomics approaches may also provide clues to personalized cancer treatments by providing useful information to the clinician about the cancer patient’s response to medical interventions. The ultimate goal of most metabolomics cancer studies is to discover cancer-specific diagnostic, prognostic or predictive biomarkers for a patient.

People infected with HIV have a substantially higher risk of some types of cancer compared with uninfected people of the same age. Three of these cancers are known as "acquired immunodeficiency syndrome (AIDS)-defining cancers" or "AIDS-defining malignancies": Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. A diagnosis of any one of these cancers marks the point at which HIV infection has progressed to AIDS. A compromised immune system can increase a person’s risk for cancer. It can also allow for cancer cells to spread faster than in someone without HIV. With the use of antiretroviral therapy (ART), the rates of AIDS-related cancers have dropped significantly. At the same time, people with HIV are at higher than average risk for several other cancers, including Hodgkin lymphoma and cancers of the anus, lung, liver, and skin, The number of cases of these other cancers is increasing in people with HIV.

The immune system is the body’s natural defence system. It is a collection of organs, cells and special molecules that helps protect you from infections, cancer and other diseases. Immuno-oncology therapies activate our immune system, making it able to recognise cancer cells and destroy them. Breast cancer is one of the major cancer types for which new immune-based cancer treatments are currently in development. Lung cancer surgery carries risks, including bleeding and infection. Clinical trials are studies of experimental lung cancer treatments. Adult central nervous system tumor is a disease in which abnormal cells form in the tissues of the brain and/or spinal cord. A tumor that starts in another part of the body and spreads to the brain is called a metastatic brain tumor. There are different types of brain and spinal cord tumors such as Astrocytic Tumors, Oligodendroglial Tumors, Mixed Gliomas, Ependymal Tumors, Medulloblastomas, Pineal Parenchymal Tumors, Meningeal Tumors, Germ Cell Tumors, Craniopharyngiom. Advances in Immuno-oncology have given oncologists and their patients reason to be encouraged—the launch of immune checkpoint inhibitors and development of other immunotherapy assets for the treatment of several difficult-to-treat diseases, including metastatic melanoma and non-small cell lung cancer, represents great progress. 

Immunotherapy encompasses several different treatment approaches, each of which has a distinct mechanism of action, and all of which are designed to boost or restore immune function in some manner.  This includes: Monoclonal antibodies, Immune checkpoint inhibitors, Therapeutic Cancer vaccines, cytokines, and other non-specific immunotherapies.