Notes single-cell OMICs in Immunotherapy (all lectures)

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




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,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.




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, 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.




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