Cancer-Associated Angiogenesis: The Endothelial Cell as a Checkpoint for Immunological Patrolling

Cancer-associated neo vessels’ formation acts as a gatekeeper that orchestrates the entrance and egress of patrolling immune cells within the tumor milieu. This is achieved, in part, via the directed chemokines’ expression and cell adhesion molecules on the endothelial cell surface that attract and retain circulating leukocytes. The crosstalk between adaptive immune cells and the cancer endothelium is thus essential for tumor immune surveillance and the success of immune-based therapies that harness immune cells to kill tumor cells. This review will focus on the biology of the endothelium and will explore the vascular-specific molecular mediators that control the recruitment, retention, and trafficking of immune cells that are essential for effective antitumor immunity. The literature revision will also explore how abnormalities in the tumor endothelium impair crosstalk with adaptive immune cells and how targeting these abnormalities can improve the success of immune-based therapies for different malignancies, with a particular focus on the paradigmatic example represented by multiple myeloma. We also generated and provide two original bio-informatic analyses, in order to sketch the physiopathology underlying the endothelial–neoplastic interactions in an easier manner, feeding into a vicious cycle propagating disease progression and highlighting novel pathways that might be exploited therapeutically

Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy

BackgroundConsolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented.MethodsA total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy.ResultsPreclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027).ConclusionMulti-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation

UV Raman Lidar Mesurements of relative Humidity for the Characterization of Aerosol and Cloud Microphysical Properties

The lidar measurements discussed in this paper were performed in Potenza (40o38’45”N, 15o48’32” - Southern Italy) by the DIFA-Univ. of BASILicata Raman lidar system (BASIL). The major feature of BASIL is its capability to perform high-resolution and accurate measurements of atmospheric temperature, both in daytime and night-time, based on the application of the rotational Raman lidar technique in the UV [1]. Besides temperature, BASIL is capable to provide measurements of particle backscatter at 355 and 532 nm, particle extinction at 355 nm, particle depolarization at 355 and water vapour mixing ratio both in daytime and night-time. Relative humidity measurements are obtained from simultaneous water vapour and temperature measurements. These parameters represents a suitable ensemble of measurements for the study of meteorological processes. Specific case studies are considered and discussed to assess relative humidity lidar measurement capability in presence of aerosols and clouds. Measurements of aerosol backscatter as a function of relative humidity are reported and discussed, highlighting the swelling tendency of hygroscopic aerosol for large relative humidity values

Rotational Raman Lidar measurementsfor the characterization of a dry stratospheric intrusion event

A UV Raman lidar system (BASIL) is operational at DIFA-Univ. of Basilicata (Potenza-Italy). The system was recently involved in LAUNCH 2005 – the International Lindenberg campaign for assessment of humidity and cloud profiling systems and its impact on high-resolution modelling - held from 12 September to 31 October 2005. During this period BASIL collected approx. 250 hours of measurements distributed over 13 Intensive Observation Periods (IOPs) and 25 days. One specific IOP was continuously run between 1-3 October 2005, covering a dry stratospheric intrusion episode associated with a tropopause folding event and the subsequent onset of perturbed weather conditions that leaded to the development of clouds and precipitations. The use of water vapour to trace stratospheric air intrusion allows to clearly identify a dry structure (approx. 1 km thick) originated in the stratosphere and descending in the free troposphere down to ~ 3 km. A similar feature is present in the temperature field, with lower temperature values observed within the dry air tongue. Relative humidity measurements reveal values as small as 0.5-1 % within the intruded air. The stratospheric origin of the observed dry layer has been verified by the application of a Lagrangian trajectory model. The subsidence of the intruding heavy dry air is most probably responsible for the gravity wave activity observed beneath the dry layer. Lidar measurements have been compared with forecasts from a MM5 mesoscale model. Comparisons in term of water vapour reveal the capability of the model to forecast the deep penetration in the troposphere of the dry intruded layer

Multiple Genetic Alterations as Resistance Mechanism during Second-Line Lorlatinib for Advanced ALK-Rearranged Lung Adenocarcinoma: A Case Report

Second and third-generation ALK-TKI inhibitors have showed better activity and have replaced crizotinib in most of cases of advanced ALK-rearranged lung adenocarcinoma. The emergence of resistance adversely affects also the activity of these newer drugs; in particular, lorlatinib often shows multiple and complex resistance mechanisms. The case reported here highlights the importance of reassessing the biomolecular profile during the disease course, both by tissutal and liquid biopsy, with the aim of improving the knowledge of these resistance mechanisms, and so identifying new drugs or sequences able to optimize the management of these patients