Tumor Immunology

Question 1

What evidence for the generation of immune responses to cancers

Answer 1

Animal Studies (memory Characteristics of B and T cells)
Histology of Human Tumors (Mononuclear cells)

Question 2

Types of Tumor antigens

Answer 2

Novel proteins encoded by mutated genes ( not many of them)
Viral encoded
Over-expressed antigen or protein eg Her2/Neu in breast cancer
Expression of proteins from repressed genes (if they are activated the proteins are re-expressed then immune system mounts attack them)
Oncofetal antigens
Differentiated antigens and glycosylated proteins

Question 3

Other caveats of Tumor antigens

Answer 3

Not very strong antigens or immunogens
Weak cells that create these antigens become tumor antigens
Less MHC 1 leads to increased tumor

Question 4

Novel tumor antigens

Answer 4

Eg MAGE in testes antigens
HER2/NEU
Tyrosinase is a normal protein in melanoma that is overexpressed
Passenger Mutation are the major source of Novel Tumor antigen

Question 5

MAGE (Melanoma Antigen Gene)

Answer 5

Normally expressed in germ-line tissues but can be expressed in different genes. In cancer cells following demethylation of gene. Presented in MHC I tumor iniatiator

Question 6

HER2/NEU

Answer 6

In breast cancer. Duplication of gene in the chromosome. Found in EGF cell proliferation
Tumor initiator
Targeted in lab monoclonal transtuzumab in treatment of HER2

Question 7

CD20 and Tyrosinase and Melanoma antigen recognized by T cells 1

Answer 7

Found in B cells. B cell cancers express CD20. It is usually targetted
Found in melanocytes in melanoma cells

Question 8

Oncofetal Antigens

Answer 8

Fetal developments
Re expressed in certain cancers
Carcinoembryonic antigen and alpha fetoprotein
Measured in blood to aid in diagnosis

Question 9

Clinical Importance of Tumor Antigens

Answer 9

Act as Immunogens usually Novel antigens
Used to detect and characterize tumor cells
Targeted for Monoclonal antibodies
Measured in blood (biomarker) eg Carcinoembryonic Antigen is oncofetal used to monitor Colon,lung,breast and pancreatic cancer rising serum indicates reoccurrence

Question 10

How does Immune system fight Caner

Answer 10

Release of cancer antigen—> present of cancer cell antigen—> priming and antivation—> traffic of T cells to tumors—> become tumors—> Recognize cancer cells by T cells —> Killing of Cancer cells

Question 11

How does Immune system fight Caner

Answer 11

NK cells: Immune surveillance
Macrophages: bind DAMPs
T cells: Most Important CD8 plays most important role but aided by CD4
B cells: Patient antibodies is useless ONLY Monoclonal antibodies matter

Question 12

How does Immune system fight Caner NK Cells

Answer 12

Immune surveillance
NK cells attach and kill tumor cells when there are few of them

Question 13

How does Immune system fight Caner Macrophages

Answer 13

Try to diffuse the situation
Depending of the macrophages will determine eg M1 Macrophages and presenting to T cells
CD4 and CD8 are involved
Cytokine for pro-inflammatory
Release ROS, NOS and ADCC have FC receptor to bind IgG
M2 Macrophages augment the ability of the tumor cells to grow eg VEGF, EGFR, TGFB

Question 14

How does Immune system fight Caner Th1

Answer 14

Play role in anti cancer immunity
Secrete gamma IFN to increase MHC 1 expression on tumor cells
Secrete IFN gamma to activate M1 macrophages
Activate CD8 (cross presentation)
IL2
Secrete pro inflammatory cytokines IL2 TNF and chemokines to allow mononuclear cells to leave blood to tumor tissue

Question 15

CD8 (cross presentation)

Answer 15

Clonal expansion to reach the tumor cells

Question 16

Suppression of Immune responses by tumor cells

Answer 16

Tregs, Th2, M2 macrophages, Myeloid - derived suppressor cells
Tumor escape immune defenses by T cells expressing CTL4, PD -1 and Tumor cells expressing PD -1L, TGF b
Tregs—> IL10 TGF b
Th2 cells inhibit Th1 via secreting IL4 and IL10
M2 macrophages and myeloid suppressor cells

Question 17

Antitumor Monoclonal Antibodies and Immune therapy

Answer 17

Anti CD20 Rituximab for B cell lymphomas
Brentuximab Vedotin for Hodgkins lymphoma; can be conjugated with chemical that disrupts microtubules
Trastuzumab tagets HER2/NEU
Blanatumomab specificity for CD19 is a chimeric antibody used for acute B cell leukemias

BCG, Anti tumor T cells, Vaccine tumor vaccine

Question 18

Immune Checkpoints Inhibitors

Answer 18

Ipilimumab is MoAB to CTLA-4
Nivolumab and Pembrolizumab is MoABS for PD-1
Avelumab and atezolizumab are MoAB for PD-1L
Trastuzumab HER2/Neu
Rituximab is CD20

Question 19

Bacillus Calmette Guerin (BCG) use in immunotherapy of bladder cancer

Answer 19

use in immunotherapy of bladder cancer

Question 20

Adoptive T cell

Answer 20

Adoptive autologous T cell therapy: cells are taken from patients and transfected and introduced back to patients
Adoptive transfer of CAR T cells: cells are taken from patient to increase its number—> chimeric receptor gens are introduced transferred back
CAR-T cells used to treat leukemias