🚨After years of work along with major funding and institutional challenges, I am proud to share this new study showing how tumor metabolism, through lactate, actively shapes immune escape.
CONTEXT
PD-1/PD-L1 blockade, such as pembrolizumab, dominates current immunotherapy. However, its efficacy in most solid tumors remains limited, and the mechanisms underlying resistance remain poorly understood.
OUR STUDY
Using breast and lung cancer cell lines, we show that chronic lactate-producing metabolic states, rather than acute glucose exposure, drive tumor-lineage–dependent immune checkpoint gene expression. Tumors do not rely on PD-L1 alone. Instead, multiple immune checkpoints including CD80, CD73, VISTA, LGALS9 (Galectin-9), CD47, and PVR are coordinately remodeled in lactate-rich environments.
By experimentally separating lactate availability from lactate production using an extracellular lactate clamp, we demonstrate that lactate-conditioned immune features persist even when endogenous glycolysis is suppressed.
WHY THIS MATTERS
These findings indicate that immune escape is multi-checkpoint and metabolically conditioned through lactate, helping explain the limited success of single-checkpoint therapies. Our study highlights tumor metabolism as an upstream regulator of immune resistance and underscores the need to target lactate production and exchange, both within and between cells, alongside immune checkpoints beyond PD-L1.
(This one´s for you Dad🙏 🕊️)
https://t.co/0uvCGoiDKm
#CancerImmunology #Immunometabolism #TumorMetabolism #ImmuneEscape #Lactate