The oldest record of cancer dates back to the period around 1600 BC, and it was Hippocrates, the Father of Medicine, who coined the term carcinos to describe several types of tumors, since these tumors and the blood vessels that radiated from them resembled a crab with its extended legs. In spite of being an old and widely-studied disease, it still poses a major challenge to the medical community. Modern techniques have enabled a better understanding of the human body as well as cancer at the molecular level opening up a plethora of options for vaccine development. Most cancer vaccines under development or in clinical trials are therapeutic vaccines that aim for tumor reduction in individuals already suffering from cancer. The arena of preventive vaccines is being explored in cancers that arise due to viruses. Given below is a description of the cancer microenvironment followed by the role of a therapeutic cancer vaccine and the strategies developed to fulfill this role. Cancerous growths in the body are composed of cancerous cells as well as a scaffold of non-cancerous cells and macromolecules. These non-cancerous components are manipulated by the cancer cells such that they provide a supporting structure for growth and nutrition of the cancerous tissue or tumor. This supporting framework is termed as cancer microenvironment. In order to develop appropriate and effective vaccines for cancer, it is essential to understand the components of a cancer microenvironment and their role in cancer growth. Most of these cell types play a vital role in wound-healing and inflammation. Cancerous growth is like a wound that never heals and secretes chemoattractants to recruit fibroblasts, endothelial cells as well as cells of the immune system to the tumor site. These cells initially try to suppress tumor progression, however, due to certain factors secreted by the cancerous cells, they promote tumor growth and progression, synthesis of new blood vessels (angiogenesis) as well as resistance to therapy. In simple terms, the soldiers and builders of the body are enslaved by the tumor to facilitate its growth and expansion. The major cell types that directly and/or indirectly interact with cancer cells have been described below, along with their role in the tumor microenvironment. These are fibroblasts, endothelial cells and mesenchymal cells that are activated by tumor-secreted factors. CAFs secrete growth factors that cause proliferation of cancerous cells, and aid the recruitment of other cell types in order to orchestrate angiogenesis and infiltration into the surrounding tissues. These are the cells that form the inner lining of blood vessels and lymphatic vessels, and are responsible for angiogenesis. Tumors activate and recruit these cells from the nearby blood vessels, and employ them to create new vessels through which the tumor can derive its nutrition as well as get rid of the cellular wastes. Leukocytes that are recruited to the tumor site include macrophages, dendritic cells (DC), neutrophils, basophils, helper T cells, cytotoxic T cells (CTL), natural killer cells, and B cells. These cells are the soldiers of our body, and are involved in mounting an immune response against foreign bodies. However, in the tumor microenvironment, these cells get manipulated, and pass on the signals for suppression of immune response against the cancer cells rather than that for destruction. The cells of a particular tissue are always embedded within a fluid matrix called extracellular matrix (ECM) that forms the supporting structure for them. The functions, shape, morphology and even survival of any cell is influenced by ECM. Hence, cancer cells directly and indirectly modify the surrounding ECM to derive nutrition, as well as to favor their proliferation, motility, and angiogenesis. Cancer cells are derivatives of normal cells and most of their molecular surface is similar to that of normal cells. It has been hypothesized that immune cells of the body, along with the signaling molecules, initially control tumor growth bringing about their targeted destruction. This phase is called the elimination phase. However, the immune system cannot completely eliminate the cancer cells, and an equilibrium phase is attained in which the immune system continues to restrict cancer growth. Although tumor progression is controlled through this phase, certain tumor cells evolve to become resistant to the immune attacks. This phase is called escape phase which is followed by tumor growth and progression since the immune cells fail to recognize tumor cells as an enemy and are not activated. Instead, the immune cells or soldiers of the body are suppressed by the tumor cells, and exploited for their benefit. A cancer vaccine aims to utilize this potential of our immune system to identify and destroy foreign cells by educating them, in vivo or ex vivo about the foreignness of cancer cells. It serves as the artificial intelligence to our immune system. In addition, cancer vaccines are also directed to alter the ECM so as to influence the survival of cancer cells. The role of a therapeutic cancer vaccine essentially involves activating the soldiers, namely dendritic cells, macrophages, cytotoxic T cells and natural killer cells to act against the tumor cells. Dendritic cells and macrophages are the professional antigen presenting cells (APCs) of the immune system. In simple terms, they eat any foreign substance encountered by them, and display antigens derived from it onto their surface. Such APCs then interact with and activate the helper and cytotoxic T cells, as well as educate them to recognize the cancerous cells. The activated T cells, in turn, multiply and activate:

• Other T cells and phagocytic cells, namely inactive macrophages and NK cells which can now directly target the cancer cells, and destroy them by cellular toxins and/or phagocytosis.
• B lymphocytes which produce antibodies specific to the tumor cells. These antibodies mark the cancer cells for destruction, and aid the macrophages and NK cells.

In addition to tumor destruction, an immune memory is also created for the tumor to avoid reformation of the same tumor. The first study surrounding the concept of a cancer vaccine was conducted in 1891 by Dr. William Coley, a bone sarcoma surgeon. However, only in the 1980s, this concept of therapeutic cancer vaccines progressed substantially. An array of cancer vaccines are currently in the different phases of research and clinical trials, and are being tested for their shortcomings, safety, and efficacy. But these studies are easier said than done, and are not devoid of practical problems and complications. Cancer still continues to be a common, and most dreaded disease of all times. Disclaimer: This Buzzle article aims to simplify the subject, and does not intend to ridicule any process, technology or person.