INTRODUCTION
Anti-PD1 immunotherapies restore anti-neoplasic immunity by limiting T cells exhaustion [1]. These new treatments have significatively modified the prognosis of metastatic or non-surgical melanoma with a 5-year survival about 50%, including side-effects and significant higher costs. For unknown reason, all patients with metastatic melanoma have not the same response to treatment.
Angiogenesis has a key role in the cancer growth. For several years, VEGF-dependent neoplasic angiogenesis has been specifically targeted to disturb neoplasic development. Despite many investigations and treatment studies, anti-angiogenic effects to prevent tumoral cells growth and metastatic development remain unsatisfactory [2]. In the early 2000’s, vasculogenic mimicry was described by Folberg et al. as a new angiogenesis-independent neoplasic vascular model [3]. Vasculogenic mimicry is an independent endothelial vascularization model, first describe in a metastatic human melanoma model by Maniotis et al[4]. At microcirculatory level, connection between endothelial and non-endothelial cells in extra-cellular matrix could increase tumoral cells exposure in blood flow (6). There are several imaging investigations to evaluate microcirculation. Among which the laser speckle contrast imaging (LSCI) and the contrast enhanced-ultrasound (CEUS). The LSCI allows a complete non-invasive screening of superficial tissue microvascularisation perfusion. It is based on the Doppler principle for measuring the speed of blood flow in tissues. By illuminating tissue with a coherent laser, it generates a pattern of light spots (speckle) whose changes in contrast are used to create two-dimensional blood perfusion maps (imaging mode) or time traces (monitoring mode), enabling analysis of blood flow in a variety of medical and scientific applications. Easy-to-use image analysis software (LDPIwin) assists in the evaluation of the results and in report generation [5]. This technic shows excellent intra and inter-observator reproductibilities [6]. The LSCI has a good spatial resolution but have never been studied for vasculogenic mimicry evaluation.
The CEUS, is a non-invasive vascular investigation, which allows a good view of neoplasic tissues and have already been validated to evaluate neoplasic microcirculation in an animal model [7] and to vascular modification due to vascular mimicry [8]. It has a high spatial and temporal resolution. Through this work, we evaluated these two imaging investigations applicabilities: laser speckle contrast imaging (LSCI) and contrast enhanced ultrasound (CEUS) in a melanoma mouse-model treated by anti-PD1.