Cancer immunology has been studied for a long time; however, the molecular and cellular basis of tumor immunity is not completely understood. Advances in understanding the basis of immunosurveillance and progress in the treatment of infectious disease have had a major impact on the development of tumor immunotherapy. The modern era of tumor immunology began in the 1950s when the role of T cell responses in tissue allograft rejection was initially identified. Since then, it has been confirmed that tumors occur in association with impaired function of T cells, indicating the importance of the immune system in the development and progression of cancer [7]. The identification of tumor-associated antigens, knowledge of effector T cell responses, and the role of regulatory and suppressor T cell populations are now shaping the use of the immune system to treat cancer.

In addition to an improved understanding of the immune system, significant advances in understanding the molecular basis of neoplasia have occurred. Precise control of cellular activity and metabolism is crucial for proper physiologic function. Notably, cell division is an important process that requires precise regulation. The main difference between tumor cells and normal cells is lack of growth control during the cell division process. This uncontrolled cell division can originate from various factors, such as chemical agents, viral infections, and mutations that lead to escape of cells from the checkpoints which properly control cell division. According to the type of tumor and proliferation rate, cancers can be benign or malignant [8]. It has been found that some tumors are caused by oncogenic viruses that induce malignant transformation. These oncogenic viruses can be both RNA and DNA viruses. Also, viral infection may lead to leukopenia and immunodeficiency, increasing the risk of malignancy. Therefore, prophylactic immunization against oncogenic viruses (such as EBV, HPV, and HBV) might be a logical strategy for prevention of malignancy [9]. Indeed, a vaccine against the human papilloma virus has shown significant impact on preventing cervical intraepithelial neoplasia and may prevent development of cervical carcinoma.

It has been reported that impaired immune response can induce tumor growth and prevent effective antitumor suppression, possibly through a process of “sneaking through” which allows improved growth of small tumors rather than large tumors [10]. Tumors may also produce immunosuppressive factors, such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and alpha-fetoprotein, which suppress innate immune responses against cancer. This has led to investigations using neutralizing antibodies against these immunosuppressive factors [7]. In contrast, tumor-specific cytotoxic T lymphocytes (CTLs) can be genetically altered to become resistant to the TGF-β inhibitory effect by transgene expression of a mutant dominant-negative TGF-ß type II receptor (DNR). In addition, specific T cells genetically manipulated to produce IL-12 can overcome the inhibitory effects of IL-10. On the other hand, tumors may express FasL and stimulate apoptosis of tumor-infiltrating effector T cells. Small interfering RNA (siRNA) can be used to knock down the Fas receptor in tumor-specific CTL, leading to a significant decrease in their susceptibility to Fas-/FasL-mediated apoptosis [11].

The interaction between the immune system and established cancers is complex, because in addition to increasing carcinogenesis by various carcinogens among compromised subjects, cancer cells themselves can lead to severe immunosuppression. It has been reported that patients involved with primary immunodeficiency syndromes have higher risk of cancer development. In a report by Kersey et al., subjects that had an inherited abnormal lymphoid system were susceptible to malignant transformation and impairment of tumor immunosurveillance [12, 13]. In addition, tumors produce soluble factors which downregulate the interleukin-2 receptor-α (IL-2Rα), leading to suppression of T cell function. Furthermore, established tumors may result in severe protein expenditures in hosts, contributing to impairment of immune system function [14].

A critical question is whether cancer cells are sufficiently different from their normal cellular counterparts, and can thus be recognized by the immune system. The immune system also produces a group of complementary markers with protective effects against cancer and other immunologic or inflammatory stresses. These markers include proteins released by T cells and are generally classified as “cytokines.” Cytokines include interleukins, interferons, tumor-necrosis factors (TNF), and lymphocyte-derived growth factors. The production of tumor-specific antibodies and/or activation of tumor antigen-specific T cells target tumor-associated antigens typically found on the cell membrane. Studies have suggested that vaccination in the presence of complements can lead to tumor lysis. While incompletely defined, several soluble and cellular mediators of tumor rejection have been described, including complement factors, active macrophages, T cells, and NK cells. While T cells require antigen specificity, the soluble and cellular mechanisms of the innate immune response can recognize the malignant phenotype in the absence of antigen specificity [15].

Since most tumor-associated antigens are self-proteins, the immune response is largely weak and patients may develop immune tolerance to tumor-associated antigens. Furthermore, the cells of the immune system may not adequately penetrate to the internal tumor microenvironment, resulting in slower immune-mediated tumor elimination. However, it is possible that the immune system may be more effective in controlling tumor growth rate rather than tumor regression [10]. Recently, it has been found that nutrition also plays a crucial role in protection against human cancer, and normal levels of zinc are required for protection against the detrimental effects of various immunosuppressive cytokines [16].

It has been found that genetic factors are as important as environmental carcinogens. Trials have tested carcinogenesis of retrovirus infection between different breeds of animals. A unique carcinogen resulted in disparate outcomes among different breeds, indicating the importance of genetic background in the progression of cancer. Environmental factors may also suppress immune responses and dysregulate immunosurveillance mechanisms [17].