Lecture 20: Cancer Immunology Flashcards
What is cancer?
Cancer: uncontrolled growth of the progeny of transformed host cells
Cancer lethality: damage and functional impairment of normal tissues
Recall the two major functions of TME.
Two major function:
- Pro-tumour
- Immunosuppression
Recall the immune surveillance theory.
The immune surveillance theory states that the immune system is constantly monitoring the body for the appearance of tumor cells, and that the majority of these aberrant cells are destroyed by the immune system before giving rise to clinically manifest tumors.
Recall the evidences to support cancer immune surveillance
- Lymphoid infiltration of cancers e.g. ‘hot’ vs. ‘cold’ tumour
- type, location, density
- Immunoscore>prognosis
- Immunodeficiency/immunosuppression
- primary (inherited) immunodeficiencies & immunodeficient mice more susceptible to cancer
- infection
- transplantation
- In vitro immune response to cancer cells
- natural killer cells
- Immune response to cancer cells in animal models (In vivo)
- mice can be immunised to tumour cells
_________________ increases risk of viral induced cancers
Recall the experimental demonstration of tumour immunity in mice models.
Recall the type of tumour antigens.
Recall how mutated/foreign antigens are presented to the immune system.
Tumour neoantigens produced by somatic mutations may change a self-protein that the patient is tolerant to (A) to one with a peptide with a new TCR contact residue that is recognized by T cells (B). Tumours caused by oncogenic viruses produce viral proteins that stimulate CD8+ T cells (C).
Recall how unmutated antigens are presented to the immune system.
Proteins that are not mutated but are expressed more abundantly by tumours than normal cells may induce T cell response in their hosts.
Many of these tumour antigens include proteins encoded by genes that are normally not expressed all in most cells of adults, because of epigenetic suppression, but are de-repressed in tumour cells, such as cancer-testis antigens (A).
Some tumour antigens may be overexpressed because of gene amplification(B).
Tissue-specific antigens are proteins expressed by both cancer cells and the normal cell types from which tumours are derived, such as tyrosinase made by both melanocytes and malignant melanoma cells. Because of either gene deregulation, or the abundance of the tumour cells, the amount of these proteins is high in the tumours, leading to T cell responses (C).
Recall the adaptive immune cells responsible for tumour immunity.
_________ can present exogenously derived Ag via the MHC-I pathway and prime CD8+ T cells.
This is possible through the process of cross-presentation.
Recall key features of CD4+ T cell help.
The antitumor effects of Th1 cells may reflect their known role in enhancing CD8+ T cell responses and activating macrophages, through the secretion of tumour necrosis factor (TNF) and interferon-γ (IFN-γ).
Recall the concept of cross-presentation by DC.
Describe personalised peptide vaccines.
Describe T regulatory cells.
Recall the role of B cells/Antibody in tumour immunity.
Recall Intratumoral TLS.
Recall the importance of NK cells in tumour immunity.
Tumour cells become susceptible to killing by NK cells when they down-regulate expression of class I MHC or they upregulate expression of ligands that bind activating NK cell receptors.
Recall the receptors of NK cells.
Recall an example where NK cells inhibit the growth of tumour cells expressing a certain surface protein.
Recall the mechanism of tumour immune evasion.
Describe the concept of immunoediting.
The first is the ‘elimination phase,’ in which the immune system recognizes and destroys potential tumor cells—the phenomenon previously referred to as immune surveillance
If elimination is not completely successful, what follows is an ‘equilibrium phase,’ in which tumour cells undergo mutations that aid their survival as a result of the selection pressure imposed by the immune system.
During the equilibrium phase, a process known as cancer immunoediting continuously shapes the properties of the tumour cells that survive. In the final ‘escape phase,’ tumour cells that have acquired the ability to elude the attentions of the immune system and grow unimpeded become clinically detectable.
Recall the concept of cancer immune equilibrium.
Recall the five challenges to cancer immunotherapy.
Recall the mechanism tumour immune evasion in Hodgkin lymphoma.
Recall the mechanism of tumour immune evasion against NK cells.
Recall combined therapies against tumour.
Recall the cross-presentation of antigens to CD8+ T cells by DC.
