Surveillance by the immune system is critically important in monitoring  and removing damaged and mutated cels as they arise. The ability  of the immune system to ki l cancer cels effectively is influenced by tumour immunogenicity and specificity. Many cancer antigens are poorly expressed and specific antigens can mutate, either spontaneously or in response to treatment, which can result in evasion of immune responses. In addition, the inhibitory pathways that are used to maintain self-tolerance and limit co lateral tissue damage during anti microbial immune responses can be co-opted by cancerous cels to evade immune destruction. Recognition and understanding of these immune checkpoint pathways has led to the development of a number of new treatments for cancers that are otherwise refractory to treatment. Immune checkpoint blockade enhances anti-tumour immunity by blocking down-regulators of immune activation. Immune check point inhibitors targeting CTLA-4, PD1 and PD-L1, such as ipilimimab, nivolumab, and pembrolizumab, have shown benefit in a number of tumour types, including melanoma, non-small  cel lung cancer, urothelial  cancers, colorectal malignancy and classic Hodgkin’s lymphoma. These agents can, however, have serious inflammatory side effects, with immune-related adverse events most commonly involving the skin, liver, endocrine and gastrointestinal tracts, which may be treatment  limiting. The effects of the different agents vary, with lung and thyroid involvement being more common with anti-PD1 therapy, colitis and hypophysitis being more common with anti-CTLA-4 therapy, with anti-CTLA-4 therapy-related events often being more severe. However, patients who have had a favourable response to immune checkpoint blockade but discontinue as a result of immune-related adverse events may maintain their anti-tumour response. Glucocorticoids are considered First line therapy for these side effects, with additional immune suppression if required. The development of autoimmunity reflects the importance of these pathways in the control of self-tolerance.

Another recent advance is CAR-T cell therapy, in which genetically engineered, chimaeric antigen receptor T cells are specifically developed for an individual patient, with effective reprogramming of the patient’s immune cells, which are then used to target their cancer. This has been applied to certain otherwise treatment-refractory haematological malignancies . Not only is it a very expensive treatment, but cytokine storm and subsequent antibody deficiency are predictable side effects of the CAR T-cell therapies directed at B-cell antigens, requiring management  in their own right.

مواضيع ذات صلة

دور الغدة الدرقية

عرض الانتجينات الخارقة super antigens

الخلايا العارضة للمستضدات

Mediators of Inflammation and the Interferons

Natural Killer Cells

CD4 + T lymphocytes

Properties of MHC Genes and Proteins

Structure of Class I MHC Molecules

معقدات التوافق النسيجي الكبرى ودورها في الاستجابة المناعية

اعادة تدوير الخلايا اللمفاوية Lymphocyte Recirculation

فرضية الانتقاء الوراثي او اختيار النسيلة Clonal selection hypothesis

الخلايا التائية المساعدة Helper T cells