Notes single-cell OMICs in Immunotherapy (all lectures)
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Course
Single-cell Omics In Immunotherapy
Institution
Vrije Universiteit Amsterdam (VU)
Notes from all the topics that go for the exam. With explanations and the most important figures. The contents are the following ones:
1. THE CANCER-IMMUNITY CYCLE
2. SYSTEMIC IMMUNOTHERAPY FOR SOLID TUMORS
3. IMMUNOTHERAPY MODALITIES
4. LOCAL IMMUNOTHERAPY IN CANCER
5. ALLERGEN IMMUNOTHERAPY
...
SINGLE-CELL OMICS IN
IMMUNOTHERAPY
By Maite Erguin
Main lecturer: Juan García Vallejo
Master’s in Biomedical Sciences. 2021/2022
Vrije Universiteit Amsterdam
,CONTENTS
1. THE CANCER-IMMUNITY CYCLE (6th September, R. van de Ven) ....................................................2
2. SYSTEMIC IMMUNOTHERAPY FOR SOLID TUMORS (7th September, Sarah Derks) .......................10
3. IMMUNOTHERAPY MODALITIES (7th September, Juan) ...............................................................14
4. LOCAL IMMUNOTHERAPY IN CANCER (8th September, Tanja de Gruijl) .......................................22
5. ALLERGEN IMMUNOTHERAPY (9th September, Ronald van Ree) .................................................30
6. LOCAL IMMUNOMODULATION FOR THE TREATMENT OF ASTHMA (10th September, H. Smits)..36
7. TARGETING MACROPHAGES IN SOLID CANCERS (13th September, Leila Akkari) ..........................43
8. TUMOR-TARGETING ANTIBODIES AND NEUTROPHILS (13th September, M. van Egmond) ..........50
9. SYSTEMIC IMMUNOTHERAPY OF HEMATOLOGIC CANCERS (14th September, N. van de Donk) ..54
10. CAR-T CELLS (16th September, Maria Themeli) ...........................................................................61
11. DENDRITIC CELL BASED VACCINES (16th September, Esther de Jong) ........................................70
12. IMMUNE TARGETING OF ANGIOGENESIS (20th September, Arjan Griffioen)..............................77
13. IMMUNOTHERAPY SIDE EFFECTS: CYTOKINE RELEASE SYNDROME (22nd September, Juan) ......80
14. ANTI-TNF AND B CELL TARGETING IN RHEUMATOID ARTHRITIDS (23rd September, Sander W.
Tas)...................................................................................................................................................88
15. INDUCTION OF PROTECTIVE IgA RESPONSES IN ENTERIC INFLAMMATION (24th September, Joep
Grootjans) ........................................................................................................................................96
16. CLINICAL ASPECTS OF IMMUNOTHERAPY SIDE EFFECTS (24th September, Mariette Labots) ...100
17. MONITORING: PLASMA (IN NEUROLOGICAL DISEASES) (27th September, Charlotte Teunissen)
.......................................................................................................................................................107
18. MONITORING: IMAGING OF IMMUNE TARGETS (IN RHEUMATIC DISEASES) (27th September,
Conny Van der Laken) ....................................................................................................................110
19. MONITORING: EXOSOMES (27th September, Irene Bijnsdorp) .................................................114
20. MONITORING: IMMUNOHISTOCHEMISTRY (IHC) (IN CANCER) (27th September, M.G.M.
Roemer) .........................................................................................................................................118
21. MONITORING: FACS (IN RESIDUAL DISEASE) (30th September, Jacqueline Cloos) ....................124
22.ONCOLYTIC VIRUSES (6th October, Victor van Beusechem) .......................................................130
23. TRANSLATING NOVEL IMMUNOTHERAPIES INTO A SUCCESSFUL SPIN-OFF COMPANY (11th
October, Arjan W. Griffioen) ..........................................................................................................135
1
,1. THE CANCER-IMMUNITY CYCLE (6th September, R. van de Ven)
• Key players and functions of the immune system
• The cancer immunity cycle
• What can we learn from the cancer immunity cycle
• How can we help the cancer immunity cycle to work
KEY PLAYERS AND FUNCTIONS OF THE IMMUNE
SYSTEM
• Cells of the immune system can recognize
“non-self” and “danger” and thus identify
infection and cellular stress/death, they are
educated to ignore “self”
• Cells of the immune system can exert
functions that neutralize infectious
organisms and promote tissue repair
An overview of the different cells:
NK cells are innate immune effector cells. They can reject viral infected cells and tumor cells. They
can release cytotoxic enzyme or cytokines such as IFN-gamma. Normally they induce tolerance if
you have normal healthy cells (which present MHC I, an inhibitor for NK). The NK gets activated if
the cell (infected, tumoral) downregulates its MHC I expression. Another way of activating them is
when there is increased expression of activating molecules in infected cells, which compete with
these MHC I.
2
, T cells are adaptive effectors. There are different types. They are created in the thymus and the
develop into CD4+ or CD8+ cells. If they express Foxp3 they will be differentiated into natural
regulatory T cell. Also depending on the trigger of the microenvironment they will develop into T
helper cells (either Th or induced T regulatory). (RA: retinoid acid). Regulatory T cells are inhibitors
of immunity.
Antigen (cross)presentation by dendritic cells (DCs): Dendritic cells recognize pathogens and present
an antigen in its MHC molecules to the T cells and secrete polarizing factors such as cytokines.
Depending on the cytokines that it produces, depending on the pathogen… The CD40-CD40L
stimulation further stimulate DCs (needed for their full activation). Also T cells secrete after different
polarizing factors.
3
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