ABSTRACT
Cancer immunoediting is crucial to understand the success or failure of a tumor. Immune system plays dual roles in tumor development and progression, promoting or suppressing tumor depending on tumor microenvironment and the events that lead to initiation of carcinogenesis. The immune system has potential to recognize and destroy tumors, and thus function as a primary defense mechanism against cancer. On the other hand, unresolved immune responses can result in the growth and progression of cancer. Objectives: The host immune system determines tumour fate in three phases (Elimination, Equilibrium and Escape) and ac- cording to this theory, it blocks adaptive and innate tumour responses or promotes conditions that favour tumour progression. Conclusion: The purpose of this review is to emphasise the importance of immunity in tumour promotion and suppression.
ABSTRACT
Given its state of stable proliferative inhibition, cellular senescence is primarily depicted as a critical mechanism by which organisms delay the progression of carcinogenesis. Cells undergoing senescence are often associated with the alteration of a series of specific features and functions, such as metabolic shifts, stemness induction, and microenvironment remodeling. However, recent research has revealed more complexity associated with senescence, including adverse effects on both physiological and pathological processes. How organisms evade these harmful consequences and survive has become an urgent research issue. Several therapeutic strategies targeting senescence, including senolytics, senomorphics, immunotherapy, and function restoration, have achieved initial success in certain scenarios. In this review, we describe in detail the characteristic changes associated with cellular senescence and summarize currently available countermeasures.
Subject(s)
Humans , Cellular Senescence , Carcinogenesis , Immunotherapy , Aging , Tumor MicroenvironmentABSTRACT
Mucosal-assooiated invariant T(MAIT) cells are an evolutionarily highly conserved T lymphocyte subsets with the innate functions similar to innate natural killer T(iNKT) cells. MAIT cells are defined by their invariant T cell receptors (TCR)-alpha chain and restrictive major histocompatibility complex (MHC) related protein-! (MR1) , and identify antigens through the MR1, secreting a variety of cytokines after being activated, directly or indirectly involved in the body's immune re-sponses. MAIT cells are also abundant in human peripheral blood and many tissues. They are closely related to the occurrence and development of various infectious diseases, autoimmune diseases and malignant tumors. This article mainly reviews the research on MAIT cells in tumor diseases.
ABSTRACT
This study aimed to investigate the efficacy of a bispecific antibody mAb04-MICA on human leukemia cell K562 both in vitro and vivo. mAb04-MICA was previously found to posses excellent anti-angiogenic activity, and have the ability to recruit immune surveillance in tumor microenvironment. In this study, the affinity of mAb04-MICA to VEGFR2 and NKG2D was identified by ELISA. CCK8 was used to detect the effect of mAb04-MICA on K562 proliferation. The cross reactivity of mAb04-MICA to murine VEGFR2 was determined by flow cytometry assay. To evaluate the antitumor activity of mAb04-MICA,tumor volume,tumor weight and the survival of K562 tumor-bearing nude mice were analyzed. The anti-angiogenic activity was determined by immunohisto-chemistry. The results indicated that mAb04-MICA could target to VEGFR2 and NKG2D,and inhibit K562 pro-liferation specifically. Besides,mAb04-MICA showed high binding capacity to murine VEGFR2. The bispecific antibody exhibited superior antitumor efficacy to the maternal monoclonal antibody and prolonged the survival of tumor-bearing mice. The expression of Ki-67,p-VEGFR2,VEGF and CD34 in mAb04-MICA treated group was significantly reduced. The results indicated that mAb04-MICA could attenuate the phosphorylation of VEGFR2 and impair angiogenesis of the tumor microenviroment. Therefore,mAb04-MICA could be further developed as a potential tumor targeted immunotherapeutic agent for leukemia.
ABSTRACT
El sistema inmune es capaz de realizar la detección y eliminación de células transformadas por un mecanismo fisiológico conocido como inmunovigilancia. En este proceso participa el receptor activador NKG2D presente en linfocitos T y células NK, ambos de suma relevancia en la inmunovigilancia contra el cáncer. Al reconocer el receptor NKG2D a sus ligandos (NKG2DLs) en las células que experimentan neotransformación se desencadena la respuesta lítica específica de las células linfoides citotóxicas. Asimismo, se ha descrito en diversos tipos de cáncer formas solubles de NKG2DLs que se ha demostrado son utilizadas para la evasión tumoral al saturar los receptores NKG2D presentes en las células efectoras linfoides evitando de esta manera ser reconocidas y eliminadas y, con ello escapando de la inmunovigilancia. Aunque este fenómeno de evasión inmune, donde participan algunos NKG2DLs, ha sido ya descrito y corroborado clínicamente no se ha estudiado si el receptor NKG2D está presente en las células tumorales per se ya que también podría estar implicado en subvertir la inmunovigilancia. En este trabajo se analizan evidencias recientes de que la expresión del receptor NKG2D no es exclusiva de linfocitos T y NK ya es expresado por células epiteliales tumorales tanto in vitro como in vivo. Las consecuencias de esta anómala expresión en células no linfoides tiene amplias implicaciones en la carcinogénesis que serán revisadas. También se analizan estudios clínicos recientes donde se comprueba la participación del receptor NKG2D en diferentes patologías tumorales.
The immune system is able to perform the detection and elimination of transformed cells by a mechanism known as physiological immune surveillance. This process involves the NKG2D receptor activator present in T lymphocytes and NK cells, both of paramount importance in the immune surveillance against cancer. To recognize the receptor NKG2D ligands (NKG2DLs) in cells that experience retransformation triggers the specific lithic response of the cytotoxic lymphoid cells. Also, soluble forms of NKG2DLs have been described in various types of cancer that have proven to be used for tumor evasion by saturating the NKG2D receptors present in the effector lymphoid cells thus avoiding their recognition and elimination, which makes them escape immune surveillance. Although this phenomenon of immune evasion, where some NKG2DLs participate, has already been described and corroborated, clinically, it has not been studied whether the receptor NKG2DL is present in the tumor cells per se because it could also be involved in reversing immune surveillance. This paper analyzes recent evidence that the expression of the NKG2D receptor is not lymphocyte T and NK exclusive it is already expressed by tumor epithelial cells in vitro and in vivo. Consequences of this anomalous expression in non-lymphoid cells have widespread implications in carcinogenesis, which will be revised. Recent clinical studies to prove the participation of NKG2D receptor in several tumor pathologies are analyzed.
Subject(s)
Humans , Neoplasms , Lymphocytes , Cytotoxins , CarcinogenesisABSTRACT
As a part of the central nervous system,retina shares many characters of the brain,including many of the functions and dysfunctions of microglia.Microglia plays important roles in multiple inflammatory procedures and degenerative diseases of the central nervous system and retina.Retinal microglia is involved in ocular inflammatory,age-related macular degeneration and diabetic retinopathy.These cells have also been identified in brain tumor and retinoblastoma.They can secrete various cytokines and growth factors that may contribute to the successful immune evasion and therefore promote the growth and invasion of tumor.To better understand the function of microglia is essential for us to develop the immune-based treatment strategies against central nervous system tumor and retinoblastoma.
ABSTRACT
Alpha fetoprotein(AFP) plays multi-role in regulating the growth of hepatocellular carcinoma cells, because of AFP has a complex molecular structure. AFP not only can promote the proliferation of hepatoma cells, but also can inhibit the immune response in liver cancer patients. Recently, documents showed that AFP has a capability to impair the function of dentritic cells(DCs), and AFP could induce DCs to death. AFP restrain DCs transform to matured antigen presenting cell through regulating the phenotype molecule express in the membrane of DCs, and AFP also influence the expression of tumor necrosis factor family and its receptor in lymphocytes or in hepatoma cells, AFP also could inhibit the activity of caspase in tumor cells, possesses these effects of AFP result in the hepatoma cells escape the immune surveillance.