Yan Leyfman, Medical Oncologist, Co-Founder and Executive Director of MedNews Week, shared a post on X:
“Solid tumors don’t just evade immunity – they exclude it.
For NK and T cells, the problem isn’t always recognition… it’s getting in.
This study flips the paradigm:
Instead of forcing cells to recognize tumors better, we reprogram how they navigate to them.
Using CRISPR activation screens, investigators identified metabolite-sensing GPCRs (GPR183, GPR84, GPR34, GPR18) as key drivers of immune cell trafficking toward breast and ovarian tumors.
The breakthrough:
Engineering NK and T cells with these receptors
Enhanced chemotaxis toward tumor-derived metabolites
Increased tumor infiltration
Improved tumor control (including in CAR-NK and CAR-T models)
Particularly striking:
GPR183 rewires immune cells to follow metabolic cues within the TME
Not just trafficking – transcriptomic reprogramming in a ligand-dependent manner
Why this matters:
We’ve spent years optimizing CAR design, costimulation, persistence…
But spatial biology may be the missing variable.
Tumors create metabolic gradients – this work shows we can exploit those signals as homing beacons.
Conceptual shift:
From antigen-targeting alone to biochemically guided immune navigation
This could be a foundational step toward making cell therapy actually work in solid tumors.”
Title: Engineering NK and T cells with metabolite-sensing receptors to target solid tumors
Authors: Young-Min Kim, Min K. Tsai, Chang Sun, Olivia Laveroni, Reece Villarin Akana, Kristen Frombach and Livnat Jerby
Other articles featuring Yan Leyfman on OncoDaily.
