Cover Page The handle

Cover Page

The handle

http://hdl.handle.net/1887/77741

holds various files of this Leiden University

dissertation.

Author: Beyranvand Nejad, E.

Elham Beyranvand Nejad

INVITATION

for attending the public defence of the dissertation

Mechanisms underlying success and failure

of

cancer immunotherapy

by

Elham Beyranvand Nejad on

Tuesday 10 September 2019 at

15:00

at the Academy Building of the Leiden University Rapenburg 73, 2311GJ

Leiden

followed by a reception E.Beyranvand_nejad@lumc.nl

Paranymphs Suzanne van Duikeren S.van_Duikeren@lumc.nl

Camilla Labrie

C.Labrie@lumc.nl

Mechanisms underlying success and failure

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Dedicated to my dear parents

and

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TC-1 anti-CD8 cisplatin 10 mg/kg Day 0 7 8 13 19 25 31 20 40 60 80 100 120 0 T umor size (m m 2)

Days after TC-1 tumor challenge

20 40 60

0 0 20 40 60 0 20 40 60

stimulated with TC-1 tumor cells

C3 anti-CD8 cisplatin 10 mg/kg Day 0 13 14 19 25 31 37 untreated cisplatin cisplatin + anti-CD8 * ** 40 60 0 20 60 80 100 0 20 40

Days after C3 tumor challenge

P ercent survival 80 100 untreated rechallenged ** * 40 60 0 20 60 80 100 0 20 40

Days after TC-1 tumor challenge

P ercent survival untreated cisplatin cisplatin + anti-CD8 *** ** * 40 60 0 20 60 80 100 0 20 40

Days after TC-1 tumor challenge

P ercent surviva l TNF IFN-J naive cisplatin 0.14% 0.09% 0.56% 0 0.2 0.4 0.6 0.8 1.0 _* % IFN-J + of CD8 T cells % TNF + of CD8 T cells ** naive cisplatin 0 0.2 0.4 0.6 0.8 1.0 0.62% CD 8 naive cisplatin Day TC-1 0 8 cisplatin 10 mg/kg 11 13 16 21 27 33 7 clodronate 17 anti-CD4 anti-NK untreated cisplatin cisplatin + anti-CD4 *** * ns 40 60 0 20 60 80 100 0 20 40

Days after TC-1 tumor challenge



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 Chapter 2 WT Cd70 -/-Cd80 / 00 86/ -/- Cd70/80/86 -/- normalized IFN-J production of pmel CD8 T cells JJ pp 0 0.5 1 1.5 D 0 0.5 1.0 1.5 2.0 500 1000 1500 2000 0 CD80 CD70 0 0.5 1.0 1.5 2.0 0 200 400 600 800 G

eo. Mean on D1 cells

concentration of cisplatin (Pg/ml) used to treat tumor cells

A 0 10 20 30 0 200 400 600 800 R- square= 0.9386 p-value= <0.0001 IFN-J (n g/ ml ) MFI CFSE B C % of max CFSE

+ long peptide and BMDCs

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 Chapter 2 A B Day 20 cisplatin (10 mg/kg) 0 analyze tumor C3 24 Day 14 cisplatin (10 mg/kg) 0 analyze tumor TC-1 18 C Ly6C L L F4 /80

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2

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