Electrochemotherapy in radiotherapy-resistant epidural spinal cord compression in metastatic cancer patients.

OBJECTIVE: To report efficacy and safety of percutaneous electrochemotherapy (ECT) in patients with radiotherapy-resistant metastatic epidural spinal cord compression (MESCC). MATERIAL/ METHODS: This retrospective study analyzed all consecutive patients treated with bleomycin-based ECT between February-2020 and September-2022 in a single tertiary referral cancer center. Changes in pain were evaluated with the Numerical Rating Score (NRS), in neurological deficit with the Neurological Deficit Scale, and changes in epidural spinal cord compression were evaluated with the epidural spinal cord compression scale (ESCCS) using an MRI. RESULTS: Forty consecutive solid tumour patients with previously radiated MESCC and no effective systemic treatment options were eligible. With a median follow-up of 5.1 months [1-19.1], toxicities were temporary acute radicular pain (25%), prolonged radicular hypoesthesia (10%), and paraplegia (7.5%). At 1 month, pain was significantly improved over baseline (median NRS: 1.0 [0-8] versus 7.0 [1.0-10], P < .001) and neurological benefits were considered as marked (28%), moderate (28%), stable (38%), or worse (8%). Three-month follow-up (21 patients) confirmed improved over baseline (median NRS: 2.0 [0-8] versus 6.0 [1.0-10], P < .001) and neurological benefits were considered as marked (38%), moderate (19%), stable (33.5%), and worse (9.5%). One-month post-treatment MRI (35 patients) demonstrated complete response in 46% of patients by ESCCS, partial response in 31%, stable disease in 23%, and no patients with progressive disease. Three-month post-treatment MRI (21 patients) demonstrated complete response in 28.5%, partial response in 38%, stable disease in 24%, and progressive disease in 9.5%. CONCLUSIONS: This study provides the first evidence that ECT can rescue radiotherapy-resistant MESCC.

CCR2-Dependent Recruitment of Tregs and Monocytes Following Radiotherapy Is Associated with TNFα-Mediated Resistance.

Radiotherapy (RT) represents one of the main anticancer approaches for the treatment of solid tumors. Beyond the expected direct effects of RT on tumor cells, evidence supporting the importance of an immune response to RT is growing. The balance between RT-mediated immunogenic and tolerogenic activity is ill-defined and deserves more attention. Herein, a murine model of head and neck squamous cell carcinoma was used to demonstrate that RT upregulated CCL2 chemokine production in tumor cells, leading to a CCR2-dependent accumulation of tumor necrosis factor alpha (TNFα)-producing monocytes and CCR2+ regulatory T cells (Treg). This corecruitment was associated with a TNFα-dependent activation of Tregs, dampening the efficacy of RT. Our results highlight an unexpected cross-talk between innate and adaptive immune system components and indicate CCL2/CCR2 and TNFα as potential clinical candidates to counterbalance the radioprotective action of monocyte-derived cells and Tregs, paving the way for potent combined radioimmunotherapies.

Caste discrimination in the ant Odontomachus hastatus: What role for behavioral and chemical cues?

In social insects, the maintenance of genetic colony integrity requires resident workers to recognize any intruder with a reproductive potential and to behave appropriately to minimize fitness costs. In this study, our objective was to identify the relative contribution of the behavioral patterns and chemical cues of intruders with different fertility status on their likelihood of being accepted in monogynous colonies. Using the ponerine ant Odontomachus hastatus as a model organism, we introduced non-nestmate workers, founding queens and heterospecific workers on intact nests in the field. We demonstrated that resident workers were more aggressive toward founding queens than toward non-nestmates workers originating from the same or a distant population. Lab experiments showed that the patterns of aggression did not differ substantially between chilled and live ants, which suggests that chemical cues alone allow caste discrimination. However, the absence of behavioral cues produced more variable results in the outcome of interactions. We also showed that resident workers readily accepted non-nestmate mature queens. The analysis of cuticular profiles revealed that individuals belonging to different castes and fertility status have contrasted chemical signatures. Overall, our study revealed that workers exhibit a graded behavioral response depending on the reproductive status of intruders. We discussed the observed variation in the extent of aggression in relation to the potential fitness costs associated with acceptance or rejection error of individuals differing in fertility status.

Onset of fights and mutual assessment in ant founding queens.

In animals, the progress and outcome of contests can be influenced by an individual's own condition, their opponent's condition or a combination of the two. The use of chemical information to assess the quality of rivals has been underestimated despite its central role in the regulation of social interactions in many taxa. Here, we studied pairwise contests between founding queens of the ant Lasius niger to investigate whether the decision to engage in agonistic interactions relies on self-assessment or mutual assessment. Queens modulated their aggressive behaviours depending on both their own status and their opponent's status. We found no influence of lipid stores or size on the onset of fights. However, differences in cuticular chemical signatures linked to fertility status accurately predicted the probability of behaving aggressively in pairs. Our study thus suggests that ant queens could rely on mutual assessment via chemical cues to make informed decisions about fight initiation.