by Sophie Rovers

Pleural mesothelioma (PM), an aggressive cancer often associated with asbestos exposure, lacks effective treatment options and has poor patient prognosis. The development of more effective treatment strategies is therefore crucial. Combining  immune checkpoint blockade and anti-angiogenic therapy to target multiple cancer hallmarks is a promising approach and has shown synergistic effects in other cancer types. In this study, we investigated the impact of combined inhibition of PD-L1 and VEGFR2 in a mouse model of PM. Using the AE17 C57BL/6 mesothelioma mouse model, we studied the effect of anti-PD-L1 combined with induction, concomitant, or consolidation anti-VEGFR2 treatment.
We demonstrated a significant tumour growth delay and survival benefit with induction and concomitant therapies. Flow cytometry revealed signs of immunosuppression and cytotoxic T cell exhaustion in the monotherapy and consolidation treatment groups, consistent with our in vivo observations. Further exploration of the intra-tumoral vasculature revealed signs of vascular normalisation in response to the combination therapy. Overall, our findings identified a good treatment schedule for combined PD-L1 and VEGFR2 inhibition and offer insights into the effects on the PM TME.

by Kaat Verbelen

Breast cancer related lymphedema or BCRL is due to its chronicity an extremely dreaded complication after breast cancer treatment. The incidence rate of objective BCRL is declining due to the major shift into the treatment approach of breast cancer. However, prevalence rate of subjective BCRL is much higher than that of objective BCRL. Subjective BCRL is defined as the diagnosis of BCRL based on the patient’s sensation of a difference in size at the upper extremity and/or trunk without any objectively measurable swelling. At this moment, it is not clear how many breast cancer patients experience subjective BCRL and what the underlying mechanisms may be. We hypothesize that four mechanisms might be associated with the presence and the severity of subjective BCRL, including sensory processing problems (1. nociceptive and/or 2. neuropathic and/or 3. central) and the presence of disturbed lymphatic transport without clinical manifestation (4. subclinical BCRL). To understand who and why patients after breast cancer treatment report subjective BCRL, a multi-center longitudinal study will be performed. This will be the first study investigating the prevalence and underlying mechanisms of subjective BCRL at different time points (starting pre-surgery up to 6 months post-radiotherapy), using state-of-the art and innovative assessment methods for both different types of BCRL and their underlying mechanisms.

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by Nicolò Filippi

The serine protease FAP (fibroblast activation protein), is an excellent biomarker for tissue remodeling processes. It is negligibly expressed in healthy adult tissues, and abundant on the surface of activated fibroblasts associated with tissue remodeling processes, such as cancer-associated-fibroblasts (CAFs) in more than 90% of epithelial tumors.
The umbrella term cancer refers to a wide spectrum of uncontrolled growths, each with its own markers. As such, radiolabelled derivatives of FAP inhibitors (FAPIs) have exciting potential as quasi-universal theranostic agents. We synthesized the first druglike ¹⁸F-labelled FAPIs for PET imaging, among which UAMC-4522 showed excellent selectivity and biodistribution, and produced PET images with remarkable resolution. Thanks to its druglikeness, UAMC-4522 has potential for further studies also outside of the oncology field, such as fibrotic disease.