BIO 343 Lecture 17: Chapter 17 Notes
Immunology Chapter 17: Immunotherapies for Cancer
Hayden Casassa
• Cancer arises from a single cell that accumulated (5+) mutations, that leads to uncontrollable growth
o Most tumors are monoclonal
o Certain mutations have to occur for cell to abolish normal controls on cell division
• Typical series of mutations of cancer
o Normal→ Adenoma→Carcinoma→Metastasis
• Cancers arise most commonly in tissues that are actively undergoing cell division and therefore more likely
to accumulate mutations
• Benign Tumors
o Encapsulated and localized
o Limited in size and slow growth rate
• Malignant Tumors
o Continuously increases in size by invading nearby tissues
o Metastatic→ cancer cells carried by lymph or blood to new tissues
▪ This starts new foci of cancer growth
o Slow or Rapid growth
o Often terminal
• 5 Main Types of Cancers
o Carcinoma→ epithelial cells
o Sarcoma→ tissue
o Leukemia→ circulating cells
o Lymphoma→ solid lymphoid tumors
o Myeloma → plasma cells in bone marrow
• All cancer-causing cells have seven key features in common
o Most important is they can evade and outrun the immune response
▪ However, only minority defeat immune system
• Two major functions of immune system
o Protection against infectious disease by recognizing and defending from pathogen
o Cancer immunosurveillance
▪ Detet ad kill aer ells hih our od does ell ith… Ho do e ko?
▪ Ppl with iuodefiie’s are ore likel to get aer
▪ Transplant patients taking immunosuppressive drugs have increased incidence of cancer
• Tumor antigens
o Malignant transformation alters protein expression in cancer cells such that they appear foreign
▪ As they look different to normal cells they are antigenic and stimulate adaptive immune
response (However some normal proteins are still made)
▪ These different antigens are called tumor antigens
• Classification of Tumor antigens
o Tumor-specific antigens
▪ Antigens present on tumor cells but not on normal cells
o Tumor-associated antigens
▪ Antigens expressed both on tumor cells and normal cells
▪ Normal cells often express smaller amounts of the antigen and go undetected
• Immune Responses to cancer have similarities with those to virus-infected cells
o Mechanism that NK cells and CD8 T cell use with lytic granules is the same
o Ab-producing B cell differs than above
• Cytotoxic T cells (CD8 cells)
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o These cells kill cancer cells similar to how they kill viral-infected cells
▪ Many tumor cells have reduced MHC class 1 reducing destruction by CD8 cells
• NK cells
o Lymphocyte that can recognize and kill cancer and virally-infected cells
o Unlike CD8 T cells, NK cells target cells that lack MHC Class 1
o Same mechanism as CD8 for killing but entirely different for recognition
o NK cells express inhibitory and activating receptors
▪ Inhibitory binds to MHC Class 1
▪ Activating binds to stress protein
o If inhibitory dominates, the NK cell activation is prevented
o If Activating from stress proteins predominates, the NK cell is activated
▪ Tumor/ infected cells have reduced MHC Class 1 and high levels of stress proteins
• Antibody-Dependent Cell-mediated Cytotoxicity (ADCC)
o NK ells epress CD6 hih ids to A’s
o When CD16 (aka FcyRI) binds to Fc region of IgG hih is oud to atige… NK ells are atiated
and release granules to induce apoptosis
• Mechanisms tumors use to escape Immunologic Destruction
o Tumors express little/no antigenic proteins
o Decreased expression of MGC class 1
o Tumor secreting immunosuppressive molecules like TGF-B
• Surgery, Radiation, and Cytotoxic Drugs are the three options to eliminate cancer
• Boostig Bod’s Poerful Iue Sste Major Caer Iuotherapies
o A’s speifi for tuor atiges
o Immune Checkpoint inhibitors
o Cancer vaccines
o Adoptive T cell transfer (ACT) and Chimeric antigen receptor (CAR) T cell therapy
• Monoclonal antibodies (mAbs) to specific tumer antigens
o Bind to tumor-associated antigens and used in conjuction
o Naked A’s
▪ Work by themselves, kill by ADCC using NK cells
o Cojugated A’s
▪ Have radioactive particle or drug attached to them
▪ Radiolaeled A’s are used as hoig deie to take sustae to delier toi sustae
directly to cancer cells
• Metastatic Breast Cancer→ product of HER2 gene is overexpressed
o HER2+ protein is overexpressed
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