Following the publication of a recent article in Clinical Cancer Research, Explicyte spoke with Pr Antoine Italiano, an internationally recognized expert in early drug development, phase I oncology trials, and immuno-oncology.
In this interview, Pr Italiano discusses the current challenges of cancer immunotherapy, the role of tertiary lymphoid structures in treatment response, and how patient selection and biomarker-driven strategies may shape the future of immuno-oncology.
What are the current challenges of immunotherapy in lung cancer?
Lung cancer remains one of the leading causes of cancer-related death in Western countries. For many years, treatment options relied mainly on chemotherapy, which offered limited response rates.
The introduction of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis has significantly changed the therapeutic landscape. However, only a minority of patients currently benefit from these treatments.
The major challenge is therefore to increase the proportion of lung cancer patients who respond to immunotherapy. To achieve this, we need to better understand the biological mechanisms of resistance and develop strategies to overcome them.
Why are tertiary lymphoid structures central to this research?
For several years, our team has investigated the role of B cells in response to cancer immunotherapy.
B cells are key components of tertiary lymphoid structures, or TLS, which are organized immune aggregates found in inflamed tissues and within some tumors.
Our previous work has shown that the presence of TLS can increase the probability of response to immune checkpoint inhibitors across several cancer types.
However, not all patients with TLS-positive tumors respond to treatment. This means that additional biological mechanisms must influence whether TLS support an effective anti-tumor immune response.
What were the key findings of this recent study?
The objective of this work was to better understand why some patients with TLS-positive non-small cell lung cancer remain resistant to PD-1/PD-L1 blockade.
We focused on tumor metabolism, and more specifically on the kynurenine pathway, which is known to exert immunosuppressive effects.
Particular attention was given to indoleamine 2,3-dioxygenase, or IDO, an enzyme involved in the conversion of tryptophan into kynurenine.
Interestingly, our findings suggest that IDO activity is associated with favorable response to treatment in this patient population.
One of the novel aspects of the study is the hypothesis that IDO may contribute to the modulation of TLS activity in inflamed tumors.
What are the clinical implications of these findings?
These results suggest that combining immune checkpoint inhibitors with IDO inhibitors could be relevant in a selected subgroup of lung cancer patients with an inflamed tumor microenvironment.
This approach reflects an important step toward precision medicine in cancer immunotherapy, where therapeutic combinations are guided by the biological features of each tumor.
With appropriate patient selection, IDO inhibitors may regain clinical interest as part of rational combination strategies.
What will the future of cancer immunotherapy look like?
The future of immunotherapy will rely on precise patient selection to improve efficacy.
As knowledge in immuno-oncology continues to grow rapidly, integrative approaches will be essential to connect biological discoveries, clinical data, and therapeutic strategies.
For each patient, the goal should be to identify the optimal treatment combination based on a specific set of biomarkers.
Artificial intelligence will likely play an important role in helping integrate these complex datasets and guide more personalized cancer immunotherapy strategies.
Pr Antoine Italiano