Radiotherapy-immune crosstalk is robust but limited
Immune modulation will require targeting sets of chemokines
Dose escalation alone can’t push beyond the biological ceiling
Understanding these concepts is key to better radio-immunotherapies
9/9

This builds on models pioneered by Niels Halama and preserves real tumor architecture and cell–cell interactions, letting us study SASP in a setting far closer to the patient’s tumor than cell culture.
8/9

5/ New tools
Studying SASP in humans was possible thanks to our improved patient-derived pancreatic tumor explant model — fresh tumor slices kept alive ex vivo and irradiated under controlled conditions.
7/9

4/ Conserved mechanism
Photon, proton, and carbon ion irradiation all trigger similar chemokine modules and immune recruitment patterns — underscoring shared regulatory pathways.
6/9

3/ Capped response
Chemokine release rises with dose, but only up to a plateau (~10 Gy biologically effective dose).
Even high-LET carbon ions don’t surpass this ceiling in SASP output or chemotaxis.
5/9

2/ Redundancy
This overlap means several chemokines can recruit the same immune cell subsets.
Blocking a single chemokine has limited effect — multiple targets are needed to alter recruitment.
(Inspired by
Cassandra Burdziak's work: 10.1126/science.add5327)
4/9

1/ Modular SASP
After irradiation, tumor cells release chemokines in defined “modules.”
Each module communicates with several receptors expressed on the same immune cell types.
3/9

- Radiation triggers coordinated chemokine modules (SASP)
- Multiple chemokines in each module target the same immune cells
- Chemokine release is maxed out at clinically relevant dose ranges
- A new explant model allows studying radiation-induced SASP in patient PDAC tissue.
2/9

Together we want to understand how pancreatic cancer reprograms our immune responses at the earliest stages of its development. 4/4

Direna was one of the first to show how inflammation helps pancreatic cancers develop. Tian created powerful models systems from patient-derived tissues which we can now use to study these processes in a human context. I'm just doing the computer stuff. 3/4

Talia and Teresa redefined how we treat pancreatic cancer particularly in high risk individuals, but it remains a dreadful disease. One key concept is to intercept pancreatic cancer before it develops into the aggressive disease we know from our patients. 2/4

Visually looks more like a t-sne to me ;)