Tumour Immunology

Abstract Tumour immunology is central to our understanding of the mechanisms of both tumour rejection and tumour progression. Virtually every known cell type of the immune system is represented in the tumour microenvironment, but as yet the functional significance of intratumoral effector cells is not fully understood. Moreover, the complex interactions between these immune cells within the tumour have yet to be fully elucidated. Although many individual effector cells have the capacity to kill tumour cells in vitro , they are frequently suppressed within the tumour microenvironment through a range of mechanisms. In this article, the known functions of immune effector cells within the tumour and the suppressive processes limiting the function of those cells are described. The purpose of tumour immunology should be to give us a better understanding of how to manipulate the immune system to fight cancer. Some relevant applications of tumour immunotherapy are therefore described. Key Concepts: Tumours are infiltrated by a broad range of immune cell types, all of which have demonstrable functions within the tumour microenvironment. The immune system can play a role in tumorigenesis and metastasis. The concept of immunesurveillance means that the innate and adaptive immune response is able to seek out and kill tumours, particularly at early stages in development. Cells of the innate immune system play a crucial role in both antitumorigenic and protumorigenic processes. NK, NKT and γδ T cells all have tumoricidal functions. The discovery of TAAs that make tumours immunologically different from other healthy tissues explains the ability of the adaptive immune system to recognise tumours as ‘nonself’. The current paradigm suggests that a TH1 effector response is required for effective antitumour T‐cell responses. CD8+ T cells recognise tumour cells bearing peptides derived from TAAs in the context of self‐MHC. Antibodies may play a role in the adaptive response to tumours. A number of mechanisms have been defined (such as ADCC and CDC), which are dependent on antibody responses. Monoclonal antibody therapy for cancer has shown the potential power of humoral responses. The tumour microenvironment is infiltrated by immune suppressive cells, including T‐regs, MDSCs and TAMs. These cells play a key role in both suppression of adaptive and innate responses against tumours, and also contribute towards tumour progression. Tumour cells are known to have the capacity to escape the immune response by modulating the expression of key target molecules. Over the last 30 years advances in our understanding of tumour immunology have led to an array of new cancer therapies based on manipulation of the immune system.