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
Objective To study the effect of time delay on tumor-immune system in tumor growth through theoretical approaches. Methods A mathematical model of the tumor-immune system interactions was established, and a time delay in the logistic growth term was introduced to investigate the processes of the interaction between immune system and tumor cells through qualitative analysis and numerical simulations. The relationship between the states of tumor and time delay was analyzed and the results were compared with the stages of the cancer immunoediting. Results Qualitative analysis and numerical simulations indicated that the tumor-immune system was a stable equilibrium state if the time delay was small. With the time delay increasing, the tumor-immune system entered equilibrium and escape stages of the cancer immunoediting, which described the alteration from dormant state to malignant state. Conclusions The time delay plays a key role in the interaction between immune system and tumor cells. The different time delays can result in different behaviors of tumor. The results will help to deepen clinical understanding of the tumor-immune system and provide references for the analysis and treatment of tumor.
ABSTRACT
Cancer immunoediting consists of three sequential phases: elimination, equilibrium, and escape. For colorectal adenoma-carcinoma sequence, the adenoma dysplastic progression may represent an equilibrium phase and the cancer stage as escape phase. Immune system eliminates transformed enterocytes by destroying them at first, sculpts them at the same time and selects the variants subsequently that are no longer recognized and insensitive to immune effectors, and finally induces immunosuppressive state within the tumor microenvironment that facilitates immune escape and tumor outgrowth. Immunosuppression and inflammation are the two crucial features of Pi (Spleen)-deficiency. Classic quotations, immune evidence and clinical observations suggest that Spleen (but not other organs) deficiency is the key pathogenesis of colorectal cancer (CRC) microenvironment. Weakness of old age, immunosuppressive cytokines from chronic inflammation, tumor-derived immunosuppressive factors and surrendered immune cells-regulatory T cells, myeloid-derived suppressor cells and tumor associated macrophages (TAMs) constitutes CRC microenvironment of Pi-deficiency. Furthermore, excess in superficiality, such as phlegm stagnation, blood stasis and toxin accumulation are induced by chronic inflammation on the basis of asthenia in origin, an immunosuppressive state. Great masters of Chinese medicine emphasize that strengthen Pi is the chief therapeutic principle for CRC which receives good therapeutic effects. So, Pi-deficiency based syndrome is the pivotal pathogenesis of tumor microenvironment. The immunosuppressive microenvironment facilitates immune escape which play an important role in the transition from adenoma to adenocarcinoma. There are some signs that strengthen Pi based treatment has potential capacity to ameliorate tumor environment. It might be a novel starting point to explore the mechanism of strengthen Pi based therapy in the prevention and treatment of CRC through regulation of tumor environment and immunoediting.
Subject(s)
Humans , Colorectal Neoplasms , Allergy and Immunology , Immune Evasion , Immunosuppression Therapy , Spleen , Allergy and Immunology , Syndrome , Tumor Microenvironment , Allergy and ImmunologyABSTRACT
Resumen En la actualidad existen 2 teorías inmunológicas, mayormente aceptadas, que explican el origen y desarrollo del cáncer: la inmunoedición tumoral y la inflamación asociada al cáncer. En ambas participan los linfocitos T reguladores (Treg) en el proceso de carcinogénesis, progresión y metástasis. Pero la mayoría de los estudios las ubican en etapas avanzadas dentro de la inmunopatogenia. La teoría de la inmunoedición del tumor propone 3 etapas inmunopatogénicas: eliminación, equilibrio y escape. Sin embargo, estas células participan en la tolerancia periférica y homeostasis del sistema inmunitario (SI). Por lo tanto, su papel no se limita a contribuir al escape de los tumores, sino que pueden participar aún antes de la aparición de la primera célula neoplásica. Quizá la función más importante se encuentre en la etapa de equilibrio de la inmunoedición, pues en ella el papel del SI adaptativo es decisivo para el control del paso a la etapa de escape, pudiendo en algunos casos provocar la regresión espontánea. Profundizando en los conocimientos de la dinámica que muestran estas células en las etapas iniciales del cáncer, se podrán describir biomarcadores diagnósticos y pronósticos, así como blancos terapéuticos que cambien el curso de la enfermedad. En esta revisión se hace una aproximación a la participación de las Treg en el desarrollo del cáncer a través de los procesos de la inflamación e inmunoedición.
Abstract Nowadays there are two accepted theories explaining the origin and development of the cancer: Tumor Immunoediting and the inflammation associated to the cancer. In both, the participation of regulatory T cells (Treg) in the carcinogenesis, progression and metastatic processes is evident but most of the studies locate these cells in advanced stages of the immunopathogenesis of the neoplastic process. However, these cells participate in the peripheral tolerance and homeostasis of the immune system. Therefore their role is not limited to contribute in the tumor cell evasion, but rather they may participate before the first cancer cell emerges. Their most important function is probably the one involved in the equilibrium stage of the immunoediting, because in this phase the adaptive immune system is decisive for the progression into the escape stage, being able in some cases to induce a spontaneous regression of the tumor. A study in depth of the dynamics of these cells in the initial stages of the cancer can help with the identification of biomarkers for diagnosis and prognosis, as well as therapeutic targets that could change the course of cancer. In this revision an approach to the participation of the Treg in the development of cancer through inflammation and immunoediting is described.
ABSTRACT
Es cada vez mayor la evidencia experimental y clínica de que el sistema inmunitario interviene activamente en la patogénesis y el control de la progresión tumoral. Una respuesta antitumoral efectiva depende de la correcta interacción de varios componentes del sistema inmunitario, como las células presentadoras de antígeno y diferentes sub-poblaciones de linfocitos T. Sin embargo, los tumores malignos desarrollan numerosos mecanismos para evadir el reconocimiento y su eliminación por parte del sistema inmunitario. En esta revisión discutiremos algunos de esos mecanismos y posibles estrategias terapéuticas para contrarrestarlos.
Increasing evidence indicates that the immune system is involved in the control of tumor progression. Effective antitumor immune response depends on the interaction between several components of the immune system, including antigen-presenting cells and different T cell subsets. However, tumor cells develop a number of mechanisms to escape recognition and elimination by the immune system. In this review we discuss these mechanisms and address possible therapeutic approaches to overcome the immune suppression generated by tumors.
Subject(s)
Humans , Immune Tolerance/immunology , Immunotherapy/methods , Neoplasms/therapy , Tumor Escape/immunology , Myeloid Progenitor Cells , Neoplasms/immunology , T-Lymphocytes, RegulatoryABSTRACT
Human papillomavirus (HPV) infection is a common sexually transmitted infection which a majority of infected women are able to clear by mounting an effective immune response. Individuals with a suboptimal immune response may be at increased risk of persistent HPV infection leading to sequelae of various grades of dysplasias and / or associated malignancy. Both cell intrinsic and extrinsic phenomena work in concert to bring about oncogenesis. Cell intrinsic factors for cervical carcinogenesis are: integration of the viral genome into the genome of the host’s cell which correlates with the progression of low grade lesions into high grade ones, inactivation of tumor suppressor genes like p53 and pRB by HPV oncoproteins particularly E6 and E7, deregulation of cell cycle regulators, host DNA synthesis and apoptosis. Cell extrinsic elements include factors contributing towards immune tolerance; some incriminated in the multistep carcinogenesis of HPV induced cervical cancer are: immunoregulatory enzyme indoleamine 2,3-dioxygenase expressing antigen presenting cells, low numbers of invariant Natural Killer T cells, anergic cytotoxic T lymphocytes, regulatory T cells (Tregs), an immunoregulatory microenvironment comprising of increased IL10, TGFβ and reduced IL2; reduced intralesional ratios of effectors (CD4 and CD8) vs. Tregs; and different types of Tregs in the lesions of invasive squamous cell carcinoma. Notch signaling plays a crucial role in regulating T cell differentiation and activation including induction of Tregs. Increased expression of Notch receptor-Jagged 1 and number of Tregs were seen in invasive disease when compared to precancer in cervical cancer. Tregs impart their function either through cytokines or by cell to cell contact. Investigation of the consequences of interference of Notch signaling in terms of the dynamics of intratumoral Tregs in cervical cancer would be interesting.