hematology and oncology
Cellular and Molecular Basis of Cancer
The Immune System and Cancer
Cancer cells often present neoantigens on their cell surface that can be detected as "non-self" by the immune system, resulting in an attack by the immune system. When and if this immune attack is effective, a cancer may never develop. Destruction of cancer cells may be complete, in which case the cancer never appears. However, some cancers have or acquire the ability to avoid detection and/or destruction by the immune system, allowing them to proliferate. It is not clear why people with a Primary Immunodeficiencies have an increased risk of only some uncommon cancers such as melanoma, renal cell carcinoma, and lymphomas and not of more common cancers of the lung, breast, prostate, and colon. Most cancers in which the immune system is ineffective are caused by viruses. Under selective (eg, evolutionary) pressure, cancer cells can express checkpoint proteins. Checkpoint proteins are cell-surface molecules that signal to T-cells that the cell bearing them is normal and should not be attacked. An example is the programmed death ligand 1 (PD-L1) protein, which is recognized by the PD-1 molecule on T cells; when PD-L1 binds to PD-1 on a T cell, an immune attack is prevented. Cancer therapy using monoclonal antibodies termed checkpoint inhibitors, which block PD-L1 or PD-1, allow the immune system to attack protected cancer cells. Cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) is another checkpoint protein that prevents immune system attack and can be similarly blocked by a specific antibody. Because checkpoint proteins can be present on normal cells, checkpoint inhibitor therapy may also induce an autoimmune response. Genetically engineered T cells (referred to as chimeric antigen receptor T-cell [CAR-T] therapy) can also be used in immune therapy. In this process, T cells are removed from a patient and genetically modified to express receptors containing a recognition domain for a specific antigen coupled to intracellular signaling domains that activate the T cell. When the modified T cells are infused, they can attack cells bearing the target antigen. Usually, the target antigen is lineage-specific, not cancer-specific. CAR-T-cell therapy is most effective against B-cell cancers such as Acute Lymphoblastic Leukemia (ALL) , 