2- Tumor Immunology Flashcards
cancer cells
general
lost normal reg control over growth so tissue destruct or host death
-comp for nutrients, obstruct vessels, inc suscept to infection
tumor types
- carcinomas- epi cells, most common
- sarcomas- muscle, fat cells, fibros
- lymphomas- solid of lymphoid tissue
- leukemias- lymphs + hematopoietic cells
bengin tumors
- slow growth rate (malig readily metastasize)
- somewhat differentiated (malignant is undiff)
- usually encapsulated so not spread
- not fatal unless @ critical sites
tumor studies
- immune resp to tumors
- tumor antigens that induce immune resp
- effector cells that kill tumor cells
- immunologic methods to detect/dx/treat
immunosurveillance theory
immune system detects/destroys cancer daily
-imp for tumors from viruses
-majority of cancers may be preventable
tumor specific antigens
unique to particular tumor and NOT present of normal cell types
-from point muts or gene rearrange
-not common in human tumors
-immune resp targets may be altered self proteins
best option
tumor associated antigens
antigens shared by diff tumors AND found on normal tissues so not good for therapy but good for detection/monitoring
i.e. oncofetal antigens, alpha fetal protein (liver cancer), carcinoembryonic antigen (colon cancer)
oncogenic viral antigens
DNA
- EBV = B cell lymphoomas
- HPV = cervical carcinoma
- HBV = hepatocellular carcinoma
relatively immunogenic bc seen as foreign
oncogenic viral antigens
RNA
- HTLV-1 = adult T cell leukemia/lymphoma with CD4+ cells
also relatively immunogenic bc foreign
differentiation antigens
tissue specific antigens so aid in dx certain tumors/ reveal tissue of origin
i.e. CD10 for B cell tumors, CD4/8/TCR/IL-2 for T cell leukemias
antibodies vs tumors
diff for immune sys to resp to spontaneous tumors bc rarely have inflamm (don’t elicit co stimulatory moles)
-tumors don’t express unique antigenic peptides
little evidence that natural antibodies inhib tumor growth
cytotoxic T lymphocytes
CTLs
most effective vs virus induced tumors
-but also carcinomas, sarcomas
tumor infiltrating lymphocytes (TIL) in solid tumors made of anti-tumor CTL
NK cells
hematopoietic tumors + virus induced
-act by downreg of class I MHC
-enhanced by interferons, TNF-a, IL-2
NK on steroids aka IL-2 = LAK cells for enhanced killing and broadened recognition
macrophages
kill by ADCC or release of TNF-a
-TNF directly lyse tumor cells via free radicals or causing hemorrhagic necrosis of tumor blood vessels
tumor evasion
- not express MHC
- MHC proteins can’t bind tumor antigen so no presentation
- induce tolerance i.e. no costim molecules
- antitumor Ab act as blocking factors
- antigens shed by tumor bind cell surface receptors
- tumor Ag masked by mucopolysaccs
- immunosupp substances released (TGF-b)
- create immunopriv site by encasing in collagen and fibrin
cancer therapies
non immune
- surgery- reduce tumor load and remove before meta, combo drugs + radiation
- hyperthermia- destroy thru superheating body tissues
- radiotherapy- x ray or cobalt 60, best on well defined non meta tumors
- chemotherapy- inhib DNA, RNA, protein syn but immunosupp side effects fatal
radiotherapy side effects
damage to marrow and intestinal mucosa
-inc suscept to infection by destroy radiosensitive lymphs
-may induce secondary tumor formation from DNA muts
immunotherapy advantages
- specifically tailor a resp to the tumor
- fewer side effects that nonspecific therapy
- more effective vs metastasis
- tumor vaccines- inc immunogenicity or APCs, induce CTLs (melanoma)
antibody therapies
- Ab to surface immunoglobulin of B cell lymphomas
-ADCC or complement required
-problem w outgrowth of tumor cell mutants - Ab vs growth factor receptors
-i.e. herceptin/trastuzumab target HER-2 receptor blocking - Ab coupled to toxin
-i.e. bacterial, chemotherapeutic, radioisotopes must be endocytosed - bi specific
-recog tumor Ag and immune system cells
purging bone marrow tumor cells
via anti-tumor Ab + complement = tumor free source of bone marrow for autologous transplant in B cell lymphoma pts
LAK cell therapy
adoptive cellular immunotherapy
lymphokine activated killer
-peripheral blood NK cultured in high dose IL-2
-reinfused into pt to kill tumor but most success with renal cell carcinoma and malig melanoma
TIL theapy
adoptive cellulr immuno
tumor inflitrating lymphocytes
-leuks from solid tumors cultured with IL-2
chimeric antigen receptors
CARs
genetically engineered receptors with
1. Ig variable genes for tumor antigen specific binding sites
2. cytoplasmic tails for signaling domains of antigen receptors and costim moles
immune checkpoint therapy
-anti tumor lymphs dev high levels of CTLA-4 and PD-1 to inhibit anti tumor resp = immune checkpoint
use Ab to target CTLA-4 and PD1 to release T cell from checkpoint = vigorous anti tumor resp
inhibit the inhibitor
