Science

Italiano Antoine Highlights Study on Turning “Cold” Tumors Immune-Active

Italiano Antoine/LinkedIn

Aug 28, 2025, 17:59

Italiano Antoine Highlights Study on Turning “Cold” Tumors Immune-Active

Italiano Antoine, Professor of Medicine Head of Early Phase Trials Unit at the Institut Bergonié, shared a post on LinkedIn about a paper by L. Boscolo Bielo et al. published on ESMO Annals of Oncology:

“CD40 Targeting and TLS Formation – A New Horizon in Cancer Immunotherapy
One of the most exciting frontiers in cancer immunotherapy today is the ability to actively induce tertiary lymphoid structures (TLS) within tumors. TLS are organized immune hubs where B cells, T cells, and dendritic cells meet, interact, and generate a local antitumor immune response. Their presence has consistently correlated with better outcomes across cancers – but the big challenge has been: how do we therapeutically trigger them?
A new Cancer Cell paper by Osorio et al. provides a breakthrough:

An Fc-optimized CD40 agonist (2141-V11), given intratumorally, was able to induce TLS formation and drive systemic antitumor immunity – with complete responses in patients with melanoma and breast cancer. This is one of the first clinical demonstrations that CD40 targeting can actively build TLS inside human tumors.
But this is not an isolated example. For instance, Melero et al. (ESMO 2024, Annals of Oncology) reported that targeted delivery approaches such as FAP-CD40 agonists (RO7300490) can restrict CD40 stimulation to the tumor stroma. In their study, this strategy not only promoted dendritic cell maturation and local immune activation but also led to TLS induction within tumors—further supporting the idea that CD40 agonism can reprogram the tumor microenvironment into an immune-permissive niche.

Why this matters:

TLS are not just biomarkers – they can be a therapeutic goal.

CD40 agonism provides a direct way to reprogram the tumor microenvironment into an immune-permissive niche.
By safely inducing TLS, we can potentially unlock durable, systemic antitumor immunity even from local interventions.
This evolving field shows how CD40 agonists, when properly engineered and delivered, can transform ‘cold’ tumors into self-sustaining immune ecosystems. TLS-inducing strategies may become a cornerstone for next-generation immunotherapies.

Exciting times ahead – with next-phase studies emerging across multiple tumor types.”

Title: Synthetic lethality in MTAP-deleted tumors: a promising avenue through targeted disruption of the protein methylation pathway

Authors: L. Boscolo Bielo, G. Curigliano

Read the full article.

Italiano Antoine