Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Abstract

Our body is constantly exposed to pathogens or external threats, but with the immune response that our body can develop, we can fight off and defeat possible attacks or infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as the existence of a tumour also cause our immune system (IS) to be put on alert. Indeed, the link between immunology and cancer is evident these days, with IS being used as one of the important targets for treating cancer. Our IS is able to eliminate those abnormal or damaged cells found in our body, preventing the uncontrolled proliferation of tumour cells that can lead to cancer. However, in several cases, tumour cells can escape from the IS. It has been observed that immune cells, the extracellular matrix, blood vessels, fat cells and various molecules could support tumour growth and development. Thus, the developing tumour receives structural support, irrigation and energy, among other resources, making its survival and progression possible. All these components that accompany and help the tumour to survive and to grow are called the tumour microenvironment (TME). Given the importance of its presence in the tumour development process, this review will focus on one of the components of the TME: immune cells. Immune cells can support anti-tumour immune response protecting us against tumour cells; nevertheless, they can also behave as pro-tumoural cells, thus promoting tumour progression and survival. In this review, the anti-tumour and pro-tumour immunity of several immune cells will be discussed. In addition, the TME influence on this dual effect will be also analysed.

The Role of the NLRP3 Inflammasome in HCC Carcinogenesis and Treatment: Harnessing Innate Immunity

“…Despite a recent surge in the literature of single cell analyses that demonstrate the existence of TAMs which synchronously express signatures from both the M1 and M2 macrophage clusters [54], TAMs and TANs are classically divided into two subtypes: on the one hand, M1 and N1 secrete IFN-γ and IL-12, potentiating the effector compartment of the cellular immunity, evading tumor growth; on the other hand, the M2 and N2 phenotypes, which are associated with the secretion of IL-4, IL-10 and TGF-β, induce an Th2 immunologic response [50,55,56]. The exact mechanisms by which TAMs, TANs and their contexts regulate HCC progression have been extensively reviewed elsewhere [50,56,57]. A continuum of transitions in the synthesis and composition of HCC TME can be observed based on integral causes such as the stochastic accumulation of mutations or extrinsic stimuli (e.g., chemotherapy).…”

Engineering New Immunotherapies against Cancer using Bacterial Outer Membrane Vesicles and Supported by Preclinical Data

“…Many of the these metabolic adjustments and newfound functionalities are enabled by intracellular genomic instability as well as infiltration of innate and adaptive cells that are recruited and reprogrammed for the secretion of cytokines that promote tumor growth. 7 During the early stages of tumor formation, occurring in the presence of a normally and fully functioning host immune system, tumors also progress through a series of cellular remodeling steps (collectively referred to as "immunoediting") that eventually lead to escape from immunosurveillance. 7,8 Initially, tumor cells are subject to elimination by both innate and adaptive immune effector cells.…”

“…7 During the early stages of tumor formation, occurring in the presence of a normally and fully functioning host immune system, tumors also progress through a series of cellular remodeling steps (collectively referred to as "immunoediting") that eventually lead to escape from immunosurveillance. 7,8 Initially, tumor cells are subject to elimination by both innate and adaptive immune effector cells. However, the genetic instability of tumor cells allows them to shed many of the surface signaling proteins, including major histocompatibility I (MHC I) and over-expression of protein antigens typically either not expressed in normally differentiated tissues, or arising again from mutation of appropriately expressed proteins leading to "neoantigens".…”

“…However, the steadily growing tumor is still unable to sustain itself without creating an environment, referred to as a tumor microenvironment (TME), that not only provides the structural support and energy required for growth, but also provides additional shielding of the growing tumor from immune surveillance through direct interference of immune cell infiltration (immune exclusion) and interruption of anti-tumor effector functions of resident immune cells (immune failure). 7,[10][11][12] This has led to tumors being referred to as "cold" or "hot" tumors. Cold tumors are refractory to immunotherapy characterized by immune evasion and exclusion (Figure 1A); hot tumors are characterized by pre-existing tumor infiltration with activated tumorspecific immune cells that can respond to appropriate immunotherapeutic vaccination (Figure 1B).…”

“…Innate immune cells include macrophages, natural killer (NK) cells, natural killer T cells (NKT), and dendritic cells (DCs). 7,8,[12][13][14] Many innate immune cells can be functionally categorized into two broadly defined types depending on whether they display anti-tumor activities or tumorigenic activities. Tumor cells can elicit cytokines that reprogram innate immune cells from type 1 to type 2 phenotypes to foster tumor growth and survival.…”