Maarten van der Doelen

Chapter 3

A

Main T cells

D

Checkpoint molecules

CD8 CD4 CD3

TIM-3 TIM-1 PD-L1 PD-1 ICOS CTLA-4 TIM-3 TIM-1 PD-L1 PD-1 ICOS CTLA-4

CD3 +

CD4 + CD8 +

Memory/effector T cells

B

CD45RO

CCR7

+ + - -

- + + - + Cell type CD8 + CD4 +

+ -

-

M-MDSC PD-L1 eMDSC PD-L1 Tregs CTLA-4

C

Immunosuppressive cells

eMDSC M−MDSC Tregs

− 50

− 50

− 10 0 10 50 100

− 10 0 10

200 300

200 300

50

100

6-Month change (% of baseline)

6-Month change (% of baseline)

Supplementary figure 8. Subgroup analysis: 6-Month change estimate of immune cell subsets during radium-223 therapy in alkaline phosphatase (ALP) responding patients. The percentage change relative to baseline is calculated using a bootstrap method. Per bootstrap, a linear model is fitted on the logit transformed and normalized bootstrap sample. Subsequently, the model predictions at baseline and after six months are used to calculate the change in T cells, immunosuppressive cells and checkpoint-expressing T cells and monocytes. A . Changes in CD3 + , CD4 + , and CD8 + T cells. B . Changes in memory/effector T cells. C . Changes in immunosuppressive cells. D. Changes in checkpoint-expressing T cells and monocytes.

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