SM_281b: Tumor Immunology Flashcards
____ is the backbone of current treatment regimens for cancer
Chemotherapy is the backbone of current treatment regimens for cancer
- Relatively nonspecific cytotoxic agents
- Low likelihood of durable response
- Limited by narrow therapeutic index, significant toxicities, frequently acquired resistance
Targeted therapies for cancer aim to ___ and modulate ___
Targeted therapies for cancer aim to inhibit molecular pathways crucial for tumor growth and maintenance and modulate immune responses
Immunotherapy elicits a ___
Immunotherapy elicits a durable anti-tumor response
- Immunotherapy is a living drug
- Immune system can evolve to treat the tumor
- Immunotherapy can cure some cancers
Describe the cancer-immunity cycle
Cancer-immunity cycle
Describe the innate immune system
Innate immune system
- Non-spcific
- No need for antigens
- No memory
- Immediate response
- Transient duration
- Tissue repair
- Macrophages, dendritic cells, NK cells, neutrophils
Describe the adaptive immune system
Adaptive immune system
- Specific
- Require antigens
- Memory is generated
- Slow response
- LIfelong duration
- T cells, B cells
Describe integration of innate and adaptive immunity
Integration of innate and adaptive immunity
Neutrophils are involved in ___ and secrete ___
Neutrophils are involved in phagocytosis and debris clean up and secrete chemokines
Dendritics cells are potent ___ that ___
Dendritics cells are potent antigen-presenting cells that uptake process antigens
- Both class I and class II pathways
- Will stimulate cytotoxic T and T helper cells
Macrophages are involved in ___ and secrete ___
Macrophages are involved in phagocytosis and debris clean up and secrete cytokines
- Type I can turn on adaptive immunity
- Type II will limit adaptive immunity
Natural killer cells can ___ and secrete high levels of ___
Natural killer cells can directly kill tumor without docking to MHC and secrete high levels of IFN-gamma
- Antibodies can activate them via FC receptor
B lymphocytes are involved in ___
B lymphocytes are involved in humoral immunity
T lymphocytes are involved in ___
T lymphocytes are involved in cellular immunity
Immune surveillance involves ___
Immune surveillance involves tumor specific antigens recognized by CD8+ T cells
___ are the critical link between innate and adaptive immunity
Dendritic cells are the critical link between innate and adaptive immunity
- Activation
- Proliferation
- CTL generation
There are checks and balances between ___ and ___
There are checks and balances between tumor regression and tumor progression
Tumor regression involves the cytokines ____, ____, ____, and ____
Tumor regression involves the cytokines IL-12, IL-2, IFN-gamma, and TNF-alpha
Tumor progression involves the cytokines ___, ___, ___, and ___
Tumor progression involves the cytokines IL-4, IL-5, IL-10, and TGF-beta
Describe immunotherapies for cancer
Immunotherapies for cancer
- Cytokines / immune stimulants: interferon (alpha, beta, gamma), IL-2
- Monoclonal antibodies: many targets in multiple malignancies
- Vaccines: stimulate immune response against autologous tumor / peptides, enhances endogenous immunity to fight cancer, sipuleucel-T for prostate cancer
- Oncolytic virus
- Gene therapy / cellular therapy: replace defective mutant allele (hereditary disease) with a functional zone
- Chimeric antigen receptor (CAR) T cells
Checkpoint inhibition ___
Checkpoint inhibition increases T cell activation
Checkpoint inhibition via ____ and ____ increases T cell activation
Checkpoint inhibition via anti-PD-1 and anti-CTLA-4 antibodies increases T cell activation
___, ___, and ___ are anti-PD-1 antibodies for checkpoint inhibition
Nivolumab, pembrolizumab, and cemiplimab are anti-PD-1 antibodies for checkpoint inhibition
____ is an anti-CTLA-4 antibody for checkpoint inhibition
Ipilimumab is an anti-CTLA-4 antibody for checkpoint inhibition
Antibody mediated targeting of ___
Antibody mediated targeting of negative regulators of T cell responses
Priming phase with CTLA-4 occurs in the ___, while the effector phase with PD-1 occurs in the ___
Priming phase with CTLA-4 occurs in the lymph node, while the effector phase with PD-1 occurs in the tumor microenvironment
- Biologic rationale for combined CTLA-4 and PD-1 blockade
___ and ___ improve overall survival in melanoma
Ipilimumab and nivolumab improve overall survival in melanoma
___ is an oncolytic virus used to treat melanoma
Talimogene laherparepvec is an oncolytic virus used to treat melanoma
___ is an atypical response that can occur with immunotherapies
Pseudoprogression is an atypical response that can occur with immunotherapies
____ is an anti-PD1 used for cutaneous squamous cell carcinoma
Cemiplimab is an anti-PD1 used for cutaneous squamous cell carcinoma
Describe immune-mediated dermatologic toxicities
Immune-mediated dermatologic toxicities
- Rash
- Pustular psoriasis
- Lichen planus
- Anti-PD-1 induced demartomyositis
- Anti-PD1 and anti-CTLA-4 induced subacute cutaneous lupus erythematosus
Describe adverse events of cancer immunotherapies
Adverse events of cancer immunotherapies
- Dermatologic toxicities
- Immune mediated colitis
- Hypophysitis
- Pneumonitis
- Transverse myelitis
- Encephalitis
___ can cause dyspnea and hypoxemic respiratory failure
Ipilimumab and novolumab can cause dyspnea and hypoxemic respiratory failure
Checkpoint blockade sometimes ___
Checkpoint blockade sometimes does not work
