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.