The Role of the Immune System in Cancer - Essay Example

The Role of the Immune System in Cancer Introduction The idea that the immune system had a role in combating and preventing was proposed in the late 50s, although scientific evidence during this period only indicated the immune system’s role in fighting pathogens but not abnormal cells. However, doctors and researchers in the latter part of the 20th century identified that the risk of developing cancer increased in individuals with absent or weak immune systems. Moreover, additional evidence has since determined that individuals whose tumours had immune cells present have a better prognosis (Lakshmi et al, 2013: p825). During the process of immunosurveillance, in which T-cells and other immune cells move through the body to identify abnormalities, mutated cells may appear abnormal to the immune cells and be recognized as non-self. Thus, the immune system protects the body from cancer by eliminating abnormal cells that present abnormal protein antigens on their cell surface. Still, the tumour cells have numerous ways to get around these defences and current research is fixated on improving the ability of the immune system to identify and kill tumour cells before they proliferate, including through cancer vaccines and immunotherapy (Lakshmi et al, 2013: p825). This paper will discuss the role of cell-mediated immunity, humoral immunity, cytokines, and inflammation in the development of cancer. Immunosurveillance and Immuno-editing Cancer immunosurveillance as a theory proposes that the host’s lymphocytes play a key role as sentinels that recognize continuously expanding transformed cells, as well as eliminating them. It appears to be a critical process for the host’s protection against carcinogenesis/tumorigenesis by maintaining the regular homeostasis of the cell. Mantovani and Sica (2010: p235) also suggests that it fundamentally functions as part of a wider and more general process called immuno-editing, in which the host is protected from developing tumour immunogenicity and cancer growth through the activity of their immune system. Poschke et al (2011: p1164) posit that the process of immuno-editing is dynamic and has three major and distinct stages, the first of which is elimination where adaptive and innate cells of the immune system combine to identify tumour cells and destroy them prior to development of malignancy. A second phase is equilibrium, through which the immune system is able to contain the outgrowth of tumour cells, but cannot entirely eliminate tumour or transformed cells. The third stage is the escape phase, during which the immune system can no longer restrict outgrowth of tumour cells, leading the development of cancer (Poschke et al, 2011: p1164). The first two phases, equilibrium and elimination, are both taken as satisfactory clinical conclusions for the patient, specifically because there is either total destruction of tumour cells or the outgrowth of tumour cells is restricted (Poschke et al, 2011: p1165). Tumour cells might undergo micro-evolution during the equilibrium phase, which, in part, may facilitate transition to the escape stage. Tumour escape also occurs if the immune system breaks down due to immuno-suppression that is normally tumour-induced, or naturally due to aging. Where a transformed cell is able to reach the escape stage, it becomes cancerous and begins to express tumour-associated antigens on its cell surface. There are four main types of tumour-associated antigens that become increasingly prevalent once the immuno-editing processes fails to get rid of the transformed cells. There are those that are expressed by genes exclusively found in tumour cells, those that are encoded by mutated variants of normal genes, antigens expressed during particular phases of development, and antigens that are over-expressed in specific tumours (Poschke et al, 2011: p1167). Tumour Antigens Recognition of cancer cells is a challenging and complex problem for the host’s immune system, during which it must differentiate between neo-plastic transformation organizations and proper cellular growth (Fulop et al, 2011: p546). In this process, tumour antigens are recognized by effector cells, followed by immunity induction. Majority of tumour cells generate antigens that could either remain on the surface of the cell or be released to the blood. Some of the antigens identified in human cancers are those in colon cancer, prostate cancer, breast carcinoma, Burkett lymphoma, among others. The immune system’s key role involves the detection of these antigens to allow for later eradication by targeting. Tumour antigens can either be tumour-associated antigens or tumour-specific antigens, which are restricted relatively to cancer cells and unique to cancer cells respectively. Both of these tumour antigens are made of portions from intracellular molecules that are expressed on the surface of cells, on which they form part of the major histocompatibility complex (Fulop et al, 2011: p546). Role of Cellular Immunity in Cancer The T-lymphocyte is the primary immune cell involved in directly recognizing cancer cells and killing them. The main role of T lymphocytes is to conduct immunologic surveillance, after which they proliferate and target cancer cells that are newly transformed and to kill them after recognition of tumour antigens (Ferris et al, 2012: p730). The response of T lymphocytes to cancer cells is modulated via other immune cells, some of which need humoral antibodies present to attack the cancer cell, also referred to as antibody-dependent cellular toxicity. This, in turn, initiates various interactions that result in the death of the cancer cell. On the other hand, the suppressor T-cells plays a key role in inhibiting the immune system’s activity against cancer cells. Cytotoxic T lymphocytes, in contrast, recognize tumour antigens that are expressed on the surface of cancer cells, proceeding to lyse these cells. Tumour-associated antigens are expressed together with class I MHC molecules o the surface of the cancer cells for recognition by cytotoxic T lymphocytes. Indeed, Ferris et al (2012 p730) identifies tumour-specific cytotoxic T lymphocytes that have been found in carcinomas of the kidney and colon, as well as malignant melanomas and sarcomas. Natural killer cells or NK cells are another group of effector cells that have anti-tumour activity. However, unlike cytotoxic T lymphocytes, natural killer cells do not have receptors to detect tumour-associated antigens, although they still have the capability to recognize transformed cancer cells (Ferris et al, 2012: p732). For natural killer cells, their anti-tumour activity is defined as natural due to lack of induction by any particular tumour antigen. While the mechanisms via which natural killer cells are able to discriminate between abnormal cancer cells and normal cells is still a subject of research, Chow et al (2012: p29) suggests that class I multi histocompatibility complex molecules sequestered on the plasma membrane of normal cells prevent lysis by inhibiting the activity of natural killer cells. As a result, a decline in the level of class I multi histocompatibility complex molecules expression that is seen in majority of cancer cells could enable the activation of natural killer cells, subsequently leading to lysis of the cancer cell (Chow et al, 2012: p29). Macrophages are another class of immune cells with the capability to kill specific cancerous cells after activation through a collection of factors, such as interferons and lymphokines, of which the latter are soluble T lymphocyte products (Chow et al, 2012: p30). Macrophages are generally less effective compared to mechanisms mediated by cytotoxic T lymphocyte mechanisms. In specific conditions, the macrophage could also play a role against carcinogenesis by presenting tumour-associated antigens to T lymphocytes and stimulating immune responses that are tumour specific. Bramson et al (2012: p15) note that classically activated macrophages, especially those of the M1 type, show cytotoxic activity against cancer cells. The macrophages could collaborate with natural killer cells and T lymphocytes in anti-cancer reactivity, particularly since interferon-γ is produced by natural killer cells and T lymphocytes and potently activates macrophages. In this case, the macrophage could kill the transformed cancer cell through mechanisms akin to those used in killing microbes, such as the secretion of tumour necrosis factor or TNF and generation of reactive oxygen radicals Bramson et al (2012: p15). Dendritic cells are also important players in the body’s immune response against transformed cancer cells, especially through their antigen-presenting capabilities. Located in the lymph nodes and the skin, dendritic cells have a central role in tumour-specific immune response initiation by taking tumour associated proteins and processing them into tumour-specific antigens that are then presented to T lymphocytes to stimulate cytotoxic T lymphocyte response to the cancerous cell. In addition, O’Sullivan et al (2012: p1879) states that dendritic cells also produce cytokines that can regulate the strength and direction of the immune response, activate natural killer cells and natural killer T cells, and play a role in coordinating the body’s humoral immune response. Boyle & Kochetkova (2014: p209) also identifies the ability of dendritic cells to inhibit cell proliferation and directly affect cancer cells through cytotoxic activity. For instance, monocytes-derived dendritic cells could portend anti-cancerous activity via various members of the tumour necrosis family, such as TRAIL, FasL, lymphotoxin-α1β2, and TNF-α, as well as granzyme and/or perforin (Boyle & Kochetkova, 2014: p209). Indeed, dendritic cells are present in cancer outgrowths with high levels of these cells correlating with a better cancer prognosis. Another group of immune cells that play an important role in cancer are the myeloid-derived suppressor cells (MDSC), which are immature myeloid cells, as well as their precursors that accumulate during transformation of cancer cells, potently suppressing the immune response. Indeed, Bindea (2010: p220) posits that MDSCs play a critical role in immune responses as cellular regulators, restraining immunity to cancerous cells using a vast range of molecular mechanisms, as well as promoting progression of tumours. While the phenotypic features of MDSCs were initially quite generally defined by CD11b+ and Gr1+ co-expression, it has been shown by recent research that they are quite complex and have different cell subtypes Bindea, 2010: p220). MDSCs with immunosuppressive and variable phenotypes features have been identified in cancer patients with a wide variety of tumours, which implicates them in enabling the progression of cancer. Another set of immune cells with similar properties are the regulator T lymphocytes or suppressor T lymphocytes that prevent autoimmune reactions. These are produced when the immune response is in the active phase, especially in the presence of pathogens and abnormal cells, to restrict damage caused by the immune reaction to the host Bindea, 2010: p221). As a result, it can be concluded that they inhibit immune responses against tumours. Humoral Immunity in Cancer Unlike T lymphocyte cytotoxic immunity, it does not appear like humoral antibodies play a substantial role in protecting against transformation and growth of tumours, particularly as most antibodies are unable to recognize tumour-associated antigens. Regardless, Pardoll (2011: p67) posits that humoral bodies that are reactive with cancerous cells have been detected in cancer patients’ sera, including breast and lung carcinomas, neuroblastoma, osteosarcoma, malignant melanoma, and Burkitt lymphoma. Cytotoxic antibodies in the blood or lymph are also directed against surface tumour-associated antigens of cancer cells, which can exert anti-cancerous effects using complement fixation, as well as acting as a market for T lymphocytes to destroy tumour cells in antibody-dependent cell-mediated cytotoxicity (Pardoll, 2011: p67). In addition, enhancing antibodies, which are a specific humoral antibody population also called blocking antibodies, could also favour growth of tumours. Inflammation and Cancer Finally, there is a powerful correlation between development of tumours and immune system-induced inflammation. Chronic inflammation has been found to contribute significantly to the development of malignancy, specifically through the induction of genotoxic stress, angiogenesis, proliferation of cells, and enhancement of tissue invasion (Finn, 2012: p7). However, it is important to note that there is no mutual exclusivity between inflammation’s tumour promotion and the immune system’s actions to suppress tumour growth. In fact, Finn (2012: p7) contends that development of tumours in sarcoma needs various molecules to induce inflammation, including IL-23, IL-1B, IL-10, and MyD88, although these same molecules induce an immune response through T-lymphocytes and interferons for tumour destruction. IL-1B and MyD88 in other primary models of carcinogenicity promote the development of tumours, although they also facilitate anti-tumour immunity through the recognition of dying cancer cells. Inflammation is also crucial in the transition between the equilibrium phase and the escape phase discussed earlier, during which there is recruitment of regulatory and inflammatory immune cells to the tumour after which they are subverted to the dampening of tumour immunity. This allows for the outgrowth of the tumour and the progression of cancer (Finn, 2012: p8). Conclusion In the past fifteen to twenty years, there has been significant progress in the research into the role played by the immune system in tumorigenesis and the development of cancer, especially with regards to the collection of research evidence into the concepts of cancer immuno-editing and immunosurveillance. These concepts have been based observed protection from development of tumours induced chemically and spontaneously in mice models, as well as the identification of several targets for recognition of cancer by the immune system in humans. Drawing from recent clinical data and mice models, it has been shown in this paper that various elements of the immune system, including its pathways, effector molecules, and cells have a primary role to play in the human body’s control and suppression of tumour cells and cancer development. References Bindea, G., Mlecnik, B., Angell, H. 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