tumour immunology and immunotherapy of cancer Flashcards
tumour antigens: explain the concept of tumour-associated antigens giving named examples, and explain how they differ from tumour-specific antigens
what are tumour-associated antigens (TAA)
normal cellular proteins which are aberrantly expressed (timing, location or quantity); ectopically expressed auto-antigens
what might need to be overcome for an immune response to target tumour-associated antigens
tolerance, as they are normal self proteins
when are cancer-testes antigens (developmental antigens) silent, and when are they not
silent in normal adult tissue except in male germ cells (some expressed in placenta)
example of tumour-associated antigen family
MAGE (melanoma associated antigens) family
tumour-associated antigens: when is human epidermal growth factor receptor 2 (HER2) overexpressed
in some breast cancers
tumour-associated antigens: what membrane-associated glycoprotein is overexpressed in many cancers
mucin 1 (MUC-1)
tumour-associated antigens: when is carcinoembryonic antigen (CEA) normally expressed, and when is it overexpressed
normally expressed in foetus/embyro, but overexpressed in wide range of carcinomas
tumour-associated antigens: 3 prostate tumour-associated antigens
prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP)
tolerance induction by negative sleection in thymus: central tolerance
T cells in thymus either undergo death by neglect, negative selection, or positive selection; if positive selection -> export to periphery (can be self-MHC-restricted, self-tolerant, T-cell repertoire) -> some autoreactivity
tumour-associated antigens: differentiation (i.e. lineage-specific) auto-antigens
auto-immune reactivity against normal cells -> melanocyte/melanoma (differentiation antigens e.g. tyrosinase (melanin production): poor self-tolerance)
what auto-immune local effect are seen in melanoma patients
depigmentation due to destruction of tyrosinase in melanocytes which produce melanin
2 major problems of targeting of tumour-associated auto-antigens for T cell-mediated immunotherapy of cancer
auto-immune responses against normal tissues, immunological tolerance (normal tolerance to auto-antigens (doesn’t have reservoir to target), tumour-induced tolerance)
