Italiano Antoine, Professor of Medicine, Head of Early Phase Trials Unit at Institut Bergonié and Head of Precision Medicine at Gustave Roussy, shared a post on LinkedIn about a recent article by Rebecca Porter et al, published in Journal for ImmunoTherapy of Cancer:
“Tertiary lymphoid structures (TLS) as a predictive biomarker—now in ovarian cancer, a classic ‘immune-resistant’ setting
New open-access data in Journal for ImmunoTherapy of Cancer (Porter et al., Dec 2025) report encouraging activity of botensilimab (Fc-enhanced anti-CTLA-4) + balstilimab (anti-PD-1) in heavily pretreated, largely platinum-resistant/refractory ovarian cancer—and provide a strong biomarker signal around immune architecture.
What caught my attention: TLS.
TLS presence was strongly associated with clinical benefit (CR/PR/SD vs PD, p<0.0001). In the figure, TLS were enriched in responders / disease control, while progressive disease was predominantly TLS-negative.
Survival signal (exploratory):
Patients with TLS showed a trend toward better OS (HR 0.56), although not statistically significant (p=0.25)—likely reflecting the small sample size (TLS n=9 vs no TLS n=21).
Why this matters
Ovarian cancer has long been considered ‘cold’ for checkpoint inhibition. These data reinforce a key idea: it’s not only “which drug” but ‘which immune architecture.’ TLS may help identify the subgroup with a pre-existing, organized antitumor immune response—potentially the patients most likely to benefit from IO combinations, even in traditionally resistant tumors.
The next step is clear: prospective validation + TLS-aware patient selection strategies in randomized studies.”
Title: Botensilimab (Fc-enhanced anti–CTLA-4 antibody) plus balstilimab (anti–PD-1 antibody) in patients with treatment-refractory ovarian cancer
Authors: Rebecca Porter, Bruno Bockorny, Bradley R. Corr, Daruka Mahadevan, Breelyn A. Wilky, Anthony B. El-Khoueiry, Andrea J. Bullock, Navid Hafez, Justin Moser, Anastasia Martynova, Justin Stebbing, Bishnu Joshi, Sean Bourdelais, Chloe Delepine, Dhan Chand, Wei Wu, Benny Johnson, Joseph E. Grossman, Steven J. O’Day, Ursula A. Matulonis, Michael S. Gordon
Read the Full Article on Journal for ImmunoTherapy of Cancer
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