tumor immunology+ immunotherapy Flashcards
DIAGRAM positive antibody test
gives off BROWN colour to show antibody binding eg to tumour
why would breast cancer cause neurological disease
antibodies against tumour enter brain and cause auto-immune neurologic disease
evidence that the immune system can control tumours
autopsies have showed ppl who had cancer cells, but no symptoms patients with melanoma/skin cancer were treated and free of disease- they donated organs, but recipient developed tumour, suggesting original patient was IMMUNE to tumour, but recipient wasn’t immunosurpression increases risk of cancer men are twice as likely of DYING from cancer than women, as women have stronger immune response
what is immunosurveillance and thus significance
malignant cells controlled by immune system thus immunotherapy enhances immune system
cancer immunity cycle
cancer cell release antigens which are detected by APC’s, which go to lymph nodes and activate T cells these T cells go to tumours and infiltrate them (tumour infiltrating lymphocytes)- they recognise cancer cells and kill them this causes cancer cells to release more antigens upon death, so cycle repeats
feauture of cancer-immunity cycle and significance
at every stage there are immune activators, and INHIBITORS inhibitors are targeted in immune checkpoint blockade
problem with cancer-immunity cycle
immune selection pressure causes cancer cells with advantage eg no MHC molecule= no detection by T cells to grow
progression of tumour and response
mutation in DNA leads to cancer cells tumour growth causes inflammation, which recruits innate cells (macrophages/NK/APC’s), which then recruit B/T cells
whats required for adaptive immunity to cancer
local inflammation from tumour ie danger signal (to recruit immune cells) expression AND recognition of cancer cell antigens
problems with immune surveillance of cancer
takes tumour while to cause local inflammation ie must be big enough tumour and normal antigens often similar
T cell response to tumour
often detect tumour-specific antigens INSIDE the cancer cell
what are tumour specific antigens and example
antigens found only in tumour, not in normal cells tumour cells often have viral antigens eg EBV/HPV, or mutate cellular proteins eg fusion proteins
cancers of viral origin according to different kinds of people
cancers that occur mainly in immunosurpressed people are Kaposi sarcoma (HIV) and EBV lymphoma cancers in healthy ppl include HepB/C and HPV genital tumours
how HPV causes cancer
due to E6/7 oncoproteins of HPV (intracellular), which causes cervical cancer
main treatment against HPV
Gardasil 9 (vaccine), which has just proteins eg E6/7, NOT DNA
what are tumour-associate antigens and thus importance for our response
NORMAL cell proteins, but expressed at wrong place/time thus tolerance may need to be overcome (ie normally self reactive lymphocytes deleted, but they may be needed to attack these normal proteins)
types of tumour-associated antigens
cancer-testes antigens MAGE family (melanoma-associated antigens) HER2 (breast cancer0 prostate antigens eg PSA
what is central tolerance+ location
in thymus, those that are self reactive are deleted, and rest are self tolerant
problems with immunotherapy against tumour associated antigens with example
we already have tolerance to auto-antigens even if we can exploit this, leads to autoimmunity as well- in melanoma, leads to vitiligo (depigmentation)
types of immunotherapies
antibody therapy therapeutic vaccination immune checkpoint blockade adoptive transfer of immune cells
types of monoclonal antibody-based therapy
naked ie just antibody: anti HER2, anti EGFR (colon cancer) conjugated- either to radioactive particle (emits radiation), or to cytotoxic drug (eg anti-HER2) bispecific antibodies- specific to 2 antigens
main type of therapeutic cancer vaccination and mechanism, what type of cancer
Provenge- for advanced prostate cancer WBC extracted and fusion protein put in- then put back into body
personalised tumour-specific cancer vaccines
DNA extracted from tumour and healthy cells, and compared using genome sequencing- HLA typing also occurs, thus mutation identified, and peptide produced
immune checkpoint blockage+ mechanism
rather than stimulate responses, regulatory response inhibited antibodies produced against regulatory T cells
