Aerobic exercise impacts the tumor microenvironment by alte…

Aerobic exercise impacts the tumor microenvironment by altering CAF abundance and composition in pancreatic cancer

Riccardo Ballarò, PhD

Background/hypothesis

Methods

45 min/day at 8 m/min or 16 m/min 5 days a week

Tumor mass

• • • • • •

Peritoneal carcinomatosis

Desmoplasia

CAF abundance

(tumor volume around 30 mm 3 )

CAF subtype distribution

Cytokine expression

Results

Exercise at 8 and 16 m/min does not impact on PDAC growth, spreading and desmoplasia

Exercise at 8 and 16 m/min impacts on CAF subtype distribution in PDAC

Exercise at 8 and 16 m/min reduces the expression of CAF-related cytokines in PDAC

Exercise at 8 and 16 m/min reduces CAF abundance in PDAC

Day 32

Whole tumor

Tumor mass

iCAFs

+

NG2

CAFs

✱

1.5

Il1b

Tnf

✱

Tgfb1

✱

80000

40

✱

✱

2.0

2.5

2.0

✱

✱✱

1.0

60000

30

2.0

1.5

1.5

40000

20

1.5

0.5

1.0

1.0

1.0

20000

10

0.5

0.5

0.0

0.5

0

0

0.0

0.0

0.0

Peritoneal carcinomatosis

apCAFs

+

myCAFs

α SMA

CAFs

20

p=0.08

0.095

FACS-isolated CAFs

40000

15

Il6 ✱

100

15

✱

p=0.056

90

30000

3

✱

10

10

Fibroblasts PDPN + CD45 - EpCAM - CD31 -

80

Single cell dissociation

20000

2

5

70

5

10000

60

0

1

0

0

50

Live cells

0

Desmoplasia

myCAF/iCAF ratio

Total CAFs

Cxcl12

Masson's trichrome

Col1a1

Hyaluronic acid

25

0.054

0.08

0.07

✱✱

30

3

2.0

40

15

0.058

20

1.5

30

15

20

2

10

✱

10

1.0

20

1

10

5

5

0.5

10

0

0.0

0

0

0

0

Conclusions

PDAC

8 m/min

16 m/min

Growth and invasion

No change —

No change —

Desmoplasia

No change —

No change —

CAF abundance

Reduces

Reduces

myCAF/iCAF ratio

Increases

Increases

CAF-related cytokine expression

Reduces

Reduces

• Exercise decreases the total amount of CAFs and alters the CAF composition by increasing myCAF and reducing iCAF.

• Due to the relevance of the CAF heterogeneity in PDAC chemoresistance and immunosuppression, further studies are needed to test the synergistic effect of exercise with chemotherapy or ICB on tumor growth.

Thanks for your attention

Keri Schadler Lab

Riccardo Ballarò rballaro@mdanderson.org @BallaroRiccardo

Jonghae Lee, PhD Sumedha Pareek Hetal Patel

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